@article{Scholaert2023,

title = {Pre-print | Multi-modal profiling of biostabilized human skin modules reveals a coordinated ecosystem response to injected mRNA-1273 COVID-19 vaccine},

author = {Manon Scholaert and Mathias Peries and Emilie Braun and Jeremy Martin and Nadine Serhan and Alexia Loste and Audrey Bruner and Lilian Basso and Benoit Chaput and Eric Merle and Pascal Descargues and Emeline Pages and Nicolas Gaudenzio},

url = {https://www.biorxiv.org/content/10.1101/2023.09.22.558940v1},

year  = {2023},

date = {2023-09-27},

journal = {bioRxiv},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tauber#2023,

title = {Landscape of mast cell populations across organs in mice and humans},

author = {Marie Tauber# and Lilian Basso# and Jeremy Martin# and Luciana Bostan and Marlene Magalhaes Pinto and Guilhem R Thierry and Raïssa Houmadi and Nadine Serhan and Alexia Loste and Camille Blériot and Jasper B J Kamphuis and Mirjana Grujic and Lena Kjellén and Gunnar Pejler and Carle Paul and Xinzhong Dong and Stephen J Galli and Laurent L Reber and Florent Ginhoux and Marc Bajenoff and Rebecca Gentek and Nicolas Gaudenzio},

url = {https://pubmed.ncbi.nlm.nih.gov/37462672/},

doi = {10.1084},

year  = {2023},

date = {2023-07-18},

urldate = {2023-07-18},

journal = {Journal of Experimental Medicine},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Scholaert†2023,

title = {3D deconvolution of human skin immune architecture with Multiplex Annotated Tissue Imaging System},

author = {Manon Scholaert† and Raissa Houmadi† and Jeremy Martin† and Nadine Serhan† and Marie Tauber and Emilie Braun and Lilian Basso and Eric Merle and Pascal Descargues and Manuelle Viguier and Cécile Lesort and Benoît Chaput and Jean Kanitakis and Denis Jullien and Cristina Bulai Livideanu and Laurence Lamant and Emeline Pagès and Nicolas Gaudenzio},

url = {https://www-science-org.proxy.insermbiblio.inist.fr/doi/10.1126/sciadv.adf9491},

doi = {10.1126/sciadv.adf9491},

year  = {2023},

date = {2023-06-07},

journal = {Science Advances},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Defaye2023,

title = {The neuronal tyrosine kinase receptor ligand ALKAL2 mediates persistent pain},

author = {Manon Defaye and Mircea C. Iftinca and Vinicius M. Gadotti and Lilian Basso and Nasser S. Abdullah and Mélissa Cuménal and Francina Agosti and Ahmed Hassan and Robyn Flynn and Jérémy Martin and Vanessa Soubeyre and Gaetan Poulen and Nicolas Lonjon and Florence Vachiery-Lahaye and Luc Bauchet and Pierre Francois Mery and Emmanuel Bourinet and Gerald W. Zamponi and Christophe Altier},

url = {https://www-jci-org.proxy.insermbiblio.inist.fr/articles/view/154317},

doi = {https://doi.org/10.1172/JCI154317},

year  = {2023},

date = {2023-05-24},

journal = {The Journal of Clinical Investigation},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Starkl2023,

title = {Pre-print | Mast cell-derived BH4 is a critical mediator of postoperative pain},

author = {Philipp Starkl and Gustav Jonsson and Tyler Artner and Bruna Lenfers Turnes and Nadine Serhan and Tiago Oliveira and Laura-Marie Gail and Karel Stejskal and Keith M. Channon and Thomas Köcher and Georg Stary and Victoria Klang and Nicolas Gaudenzio and Sylvia Knapp and Clifford J. Woolf and Josef M. Penninger and Shane J.F. Cronin},

url = {https://www.biorxiv.org/content/10.1101/2023.01.24.525378v1},

year  = {2023},

date = {2023-01-24},

journal = {bioRxiv},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gaudenzio2022,

title = {Mast cell-neuron axis in allergy},

author = {Nicolas Gaudenzio, Lilian Basso},

year  = {2022},

date = {2022-05-20},

journal = {Curr Opin Immunol .},

volume = {77},

number = {102213},

pages = {1-6},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{N2022,

title = {Immune cells impede repair of old neurons},

author = {Gaudenzio N, Liblau RS.},

editor = {{Lambert de Rouvroit}, Catherine},

year  = {2022},

date = {2022-05-13},

journal = {Science},

volume = {376},

number = {6594},

pages = { 694-695},

abstract = {The regenerative capacity of older people is reduced, resulting in decreased tissue function and resilience. Accordingly, the regeneration of the sciatic nerve after injury has been reported to be less efficient and slower in older people (1). One of the hallmarks of aging is altered intercellular communication, which is often accompanied by increased density of immune cells within tissues and excessive release of proinflammatory mediators, called inflammaging (2, 3). In this context, the immune system disturbs tissue homeostasis and impedes functional recovery. However, the precise mechanisms underlying this pathophysiological process are largely elusive, which is a barrier to rational treatment design. On page 715 of this issue, Zhou et al. (4) describe a mechanism by which aged sensory neurons release the chemoattractive protein C-X-C motif chemokine ligand 13 (CXCL13). Upon sciatic nerve injury in aged, but not young, mice, this results in the recruitment of CD8+ T cells that prevent axonal regeneration.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{J2021,

title = {Neutrophil-specific gain-of-function mutations in Nlrp3 promote development of cryopyrin-associated periodic syndrome},

author = {Stackowicz J, Gaudenzio N, Serhan N, Conde E, Godon O, Marichal T, Starkl P, Balbino B, Roers A, Bruhns P, Jönsson F, Moguelet P, Georgin-Lavialle S, Broderick L, Hoffman HM, Galli SJ, Reber},

year  = {2021},

date = {2021-09-03},

journal = {J. Exp. Med },

volume = {218},

number = {10},

abstract = {Gain-of-function mutations in NLRP3 are responsible for a spectrum of autoinflammatory diseases collectively referred to as

“cryopyrin-associated periodic syndromes” (CAPS). Treatment of CAPS patients with IL-1–targeted therapies is effective,

confirming a central pathogenic role for IL-1β. However, the specific myeloid cell population(s) exhibiting inflammasome

activity and sustained IL-1β production in CAPS remains elusive. Previous reports suggested an important role for mast cells

(MCs) in this process. Here, we report that, in mice, gain-of-function mutations in Nlrp3 restricted to neutrophils, and to a lesser

extent macrophages/dendritic cells, but not MCs, are sufficient to trigger severe CAPS. Furthermore, in patients with

clinically established CAPS, we show that skin-infiltrating neutrophils represent a substantial biological source of IL-1β.

Together, our data indicate that neutrophils, rather than MCs, can represent the main cellular drivers of CAPS pathology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{E2021,

title = {Dual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice},

author = {Conde E, Bertrand R, Balbino B, Bonnefoy J, Stackowicz J, Caillot N, Colaone F, Hamdi S, Houmadi R, Loste A, Kamphuis JBJ, Huetz F, Guilleminault L, Gaudenzio N, Mougel A, Hardy D, Snouwaert JN, Koller BH, Serra V, Bruhns P, Grouard-Vogel G, Reber LL.},

doi = {10.1038/s41467-021-22834-5},

year  = {2021},

date = {2021-05-11},

journal = {Nature Communications},

volume = {12},

number = {1},

pages = {2574},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Starkl,

title = {Title: IgE antibodies increase honeybee venom responsiveness and detoxification efficiency of mast cells Authors},

author = {Starkl, Philipp and Gaudenzio, Nicolas and Marichal, Thomas and Reber, Laurent L and Sibilano, Riccardo and Watzenboeck, Martin L and Fontaine, Fr{é}d{é}ric and Mueller, Andr{é} C and Tsai, Mindy and Knapp, Sylvia and Galli, Stephen J},

doi = {10.1111/ALL.14852},

year  = {2021},

date = {2021-04-12},

abstract = {Background},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Serhan2021,

title = {Mas-related G protein-coupled receptors (Mrgprs) - Key regulators of neuroimmune interactions},

author = {Serhan, Nadine and Cenac, Nicolas and Basso, Lilian and Gaudenzio, Nicolas},

doi = {10.1016/j.neulet.2021.135724},

issn = {03043940},

year  = {2021},

date = {2021-01-01},

journal = {Neuroscience Letters},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tauber2021b,

title = {Bidirectional sensory neuron-immune interactions: a new vision in the understanding of allergic inflammation},

author = {Tauber, Marie and Wang, Fang and Kim, Brian and Gaudenzio, Nicolas and Blank, Ulrich and Kawakami, Toshiaki},

url = {https://doi.org/10.1016/j.coi.2021.03.012},

doi = {10.1016/j.coi.2021.03.012},

year  = {2021},

date = {2021-01-01},

journal = {Current Opinion in Immunology},

volume = {72},

pages = {79--86},

abstract = {Peripheral neurons (including sensory neurons) are ubiquitously distributed in all tissues, particularly at the interface with the environment. The primary function of sensory neurons is the transmission of sensations of temperature, pain and itch to elicit appropriate behavioral responses. More recently, sensory neurons have emerged as potent regulators of type 2 immune responses and allergic inflammation. There is increasing evidence showing that neurons can express receptors previously thought to be restricted to the immune compartment. In addition, certain subtypes of immune cells (e.g. mast cells, ILC2s or macrophages) also express specific neuroreceptors that provide them with the capacity to integrate neuron-derived signals and modulate their activation status during the development of allergic inflammation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {MRGPRX2 sensing of cationic compounds-A bridge between nociception and skin diseases?},

author = {Corbière, A. and Loste, A. and Gaudenzio, N.},

year  = {2021},

date = {2021-01-01},

journal = {Exp Dermatol},

volume = {30},

number = {2},

pages = {193-200},

abstract = {Mast cells are innate immune cells located at many barrier sites in the body and known to protect the host against environmental threats and to be involved in allergic diseases. More recently, new studies have investigated their roles in the regulation of skin inflammation and transmission of pain and itch sensations. Mast cell signalling through the Mas-related G protein-coupled receptor (MRGPR) X2 or its mouse orthologue MRGPRB2 has been reported to be one of the major mechanism by which mast cell can regulate such processes. MRGPRX2 and MRGPRB2 can induce mast cell degranulation upon binding to a broad panel of cationic molecules such as neuropeptides, bacteria-derived quorum sensing molecules, venom peptides, host defense peptides and, unfortunately, various FDA-approved drugs. Upon activation, mast cells release granule-associated proteases, lipids and multiple cytokines that can modulate vascular permeability, immune cells recruitment and activation status of tissue-projecting nociceptive sensory neurons (ie nociceptors). Here, we discuss the modality of MRGPRX2-dependent mast cell activation and its different consequences on the patterns of skin inflammation and associated diseases. We notably emphasize how MRGPRX2-dependent skin mast cell activation might trigger various pathological traits such as pruritus, pain and inflammation and therefore become a potential therapeutic target for inflammatory pain, itch, atopic dermatitis and drugs-induced injection site reactions.},

note = {Corbière, Auriane 

Loste, Alexia 

Gaudenzio, Nicolas 

802041/H2020 European Research Council/ 

Review 

Denmark 

Exp Dermatol. 2021 Feb;30(2):193-200. doi: 10.1111/exd.14222. Epub 2020 Nov 17.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Mas-related G protein-coupled receptors (Mrgprs) - Key regulators of neuroimmune interactions},

author = {Serhan, N. and Cenac, N. and Basso, L. and Gaudenzio, N.},

year  = {2021},

date = {2021-01-01},

journal = {Neurosci Lett},

volume = {749},

pages = {135724},

abstract = {Interplay between physiological systems in the body plays a prominent role in health and disease. At the cellular level, such interplay is orchestrated through the binding of specific ligands to their receptors expressed on cell surface. G protein-coupled receptors (GPCR) are seven-transmembrane domain receptors that initiate various cellular responses and regulate homeostasis. In this review, we focus on particular GPCRs named Mas-related G protein-coupled receptors (Mrgprs) mainly expressed by sensory neurons and specialized immune cells. We describe the different subfamilies of Mrgprs and their specific ligands, as well as recent advances in the field that illustrate the role played by these receptors in neuro-immune biological processes, including itch, pain and inflammation in diverse organs.},

note = {Serhan, Nadine 

Cenac, Nicolas 

Basso, Lilian 

Gaudenzio, Nicolas 

Research Support, Non-U.S. Gov't 

Review 

Ireland 

Neurosci Lett. 2021 Apr 1;749:135724. doi: 10.1016/j.neulet.2021.135724. Epub 2021 Feb 15.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {IgE antibodies increase honeybee venom responsiveness and detoxification efficiency of mast cells},

author = {Starkl, P. and Gaudenzio, N. and Marichal, T. and Reber, L. L. and Sibilano, R. and Watzenboeck, M. L. and Fontaine, F. and Mueller, A. C. and Tsai, M. and Knapp, S. and Galli, S. J.},

year  = {2021},

date = {2021-01-01},

journal = {Allergy},

abstract = {BACKGROUND: In contrast to their clearly defined roles in allergic diseases, the physiologic functions of Immunoglobulin E antibodies (IgEs) and mast cells (MCs) remain enigmatic. Recent research supports the toxin hypothesis, showing that MCs and IgE-related type 2 immune responses can enhance host defense against certain noxious substances, including honeybee venom (BV). However, the mechanisms by which MCs can interfere with BV toxicity are unknown. In this study, we assessed the role of IgE and certain MC products in MC-mediated BV detoxification. METHODS: We applied in vitro and in vivo fluorescence microscopyimaging, and flow cytometry, fibroblast-based toxicity assays and mass spectrometry to investigate IgE-mediated detoxification of BV cytotoxicity by mouse and human MCs in vitro. Pharmacologic strategies to interfere with MC-derived heparin and proteases helped to define the importance of specific detoxification mechanisms. RESULTS: Venom-specific IgE increased the degranulation and cytokine responses of MCs to BVin vitro. Passive serum sensitization enhanced MC degranulation in vivo. IgE-activated mouse or human MCs exhibited enhanced potential for detoxifying BV by both proteolytic degradation and heparin-related interference with toxicity. Mediators released by IgE-activated human MCs efficiently degraded multiple BV toxins. CONCLUSIONS: Our results both reveal that IgE sensitization enhances the MC's ability to detoxify BV and also assign efficient toxin-neutralizing activity to MC-derived heparin and proteases. Our study thus highlights the potential importance of IgE, MCs, and particular MC products in defense against BV.},

note = {Starkl, Philipp 

Gaudenzio, Nicolas 

Marichal, Thomas 

Reber, Laurent L 

Sibilano, Riccardo 

Watzenboeck, Martin L 

Fontaine, Frédéric 

Mueller, André C 

Tsai, Mindy 

Knapp, Sylvia 

Galli, Stephen J 

Fondation Acteria/ 

J3399-B21/Austrian Science Fund/ 

P31113-B30/Austrian Science Fund/ 

655153/H2020 Marie Skłodowska-Curie Actions/ 

F.4508.18/Fonds De La Recherche Scientifique - FNRS/ 

Institut National de la Santé et de la Recherche Médicale/ 

R01 AI070813/AI/NIAID NIH HHS/United States 

R01 AI132494/AI/NIAID NIH HHS/United States 

R01 AI23990/National Institute of Allergy and Infectious Diseases/ 

R01 AR067145/AR/NIAMS NIH HHS/United States 

ANR-18-CE18-0023/Agence Nationale de la Recherche/ 

ERC-StG-2018 IM-ID #801823/ERC/ 

ERC-StG-2018 IM-ID #802041/ERC/ 

Denmark 

Allergy. 2021 Apr 11. doi: 10.1111/all.14852.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Bidirectional sensory neuron-immune interactions: a new vision in the understanding of allergic inflammation},

author = {Tauber, M. and Wang, F. and Kim, B. and Gaudenzio, N.},

year  = {2021},

date = {2021-01-01},

journal = {Curr Opin Immunol},

volume = {72},

pages = {79-86},

abstract = {Peripheral neurons (including sensory neurons) are ubiquitously distributed in all tissues, particularly at the interface with the environment. The primary function of sensory neurons is the transmission of sensations of temperature, pain and itch to elicit appropriate behavioral responses. More recently, sensory neurons have emerged as potent regulators of type 2 immune responses and allergic inflammation. There is increasing evidence showing that neurons can express receptors previously thought to be restricted to the immune compartment. In addition, certain subtypes of immune cells (e.g. mast cells, ILC2s or macrophages) also express specific neuroreceptors that provide them with the capacity to integrate neuron-derived signals and modulate their activation status during the development of allergic inflammation.},

note = {Tauber, Marie 

Wang, Fang 

Kim, Brian 

Gaudenzio, Nicolas 

Review 

England 

Curr Opin Immunol. 2021 Apr 16;72:79-86. doi: 10.1016/j.coi.2021.03.012.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Conde2021,

title = {Dual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice},

author = {Eva Conde and Romain Bertrand and Bianca Balbino and Jonathan Bonnefoy and Julien Stackowicz and Noémie Caillot and Fabien Colaone and Samir Hamdi and Raïssa Houmadi and Alexia Loste and Jasper B. J. Kamphuis and François Huetz and Laurent Guilleminault and Nicolas Gaudenzio and Aurélie Mougel and David Hardy and John N. Snouwaert and Beverly H. Koller and Vincent Serra and Pierre Bruhns and Géraldine Grouard-Vogel and Laurent L. Reber},

url = {http://www.nature.com/articles/s41467-021-22834-5},

doi = {10.1038/s41467-021-22834-5},

issn = {2041-1723},

year  = {2021},

date = {2021-01-01},

journal = {Nature Communications},

volume = {12},

pages = {2574},

abstract = {<p>Allergic asthma is characterized by elevated levels of IgE antibodies, type 2 cytokines such as interleukin-4 (IL-4) and IL-13, airway hyperresponsiveness (AHR), mucus hypersecretion and eosinophilia. Approved therapeutic monoclonal antibodies targeting IgE or IL-4/IL-13 reduce asthma symptoms but require costly lifelong administrations. Here, we develop conjugate vaccines against mouse IL-4 and IL-13, and demonstrate their prophylactic and therapeutic efficacy in reducing IgE levels, AHR, eosinophilia and mucus production in mouse models of asthma analyzed up to 15 weeks after initial vaccination. More importantly, we also test similar vaccines specific for human IL-4/IL-13 in mice expressing human IL-4/IL-13 and the related receptor, IL-4Rα, to find efficient neutralization of both cytokines and reduced IgE levels for at least 11 weeks post-vaccination. Our results imply that dual IL-4/IL-13 vaccination may represent a cost-effective, long-term therapeutic strategy for the treatment of allergic asthma as demonstrated in mouse models, although additional studies are warranted to assess its safety and feasibility.</p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Starkl2020,

title = {IgE Effector Mechanisms, in Concert with Mast Cells, Contribute to Acquired Host Defense against Staphylococcusaureus.},

author = {Starkl, Philipp and Watzenboeck, Martin L and Popov, Lauren M and Zahalka, Sophie and Hladik, Anastasiya and Lakovits, Karin and Radhouani, Mariem and Haschemi, Arvand and Marichal, Thomas and Reber, Laurent L and Gaudenzio, Nicolas and Sibilano, Riccardo and Stulik, Lukas and Fontaine, Fr{é}d{é}ric and Mueller, Andr{é} C and Amieva, Manuel R and Galli, Stephen J and Knapp, Sylvia},

doi = {10.1016/j.immuni.2020.08.002},

issn = {1097-4180 (Electronic)},

year  = {2020},

date = {2020-10-01},

journal = {Immunity},

volume = {53},

number = {4},

pages = {793--804.e9},

abstract = {Allergies are considered to represent mal-directed type 2 immune responses against mostly innocuous exogenous compounds. Immunoglobulin E (IgE) antibodies are a characteristic feature of allergies and mediate hypersensitivity against allergens through activation of effector cells, particularly mast cells (MCs). Although the physiological functions of this dangerous branch of immunity have remained enigmatic, recent evidence shows that allergic immune reactions can help to protect against the toxicity of venoms. Because bacteria are a potent alternative source of toxins, we assessed the possible role of allergy-like type 2 immunity in antibacterial host defense. We discovered that the adaptive immune response against Staphylococcus aureus (SA) skin infection substantially improved systemic host defense against secondary SA infections in mice. Moreover, this acquired protection depended on IgE effector mechanisms and MCs. Importantly, our results reveal a previously unknown physiological function of allergic immune responses, IgE antibodies, and MCs in host defense against a pathogenic bacterium.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Jendoubi2020b,

title = {Omalizumab in the treatment of adult patients with mastocytosis: A systematic review.},

author = {Jendoubi, Fatma and Gaudenzio, Nicolas and Gallini, Adeline and Negretto, Mathilde and Paul, Carle and {Bulai Livideanu}, Cristina},

doi = {10.1111/cea.13592},

issn = {1365-2222 (Electronic)},

year  = {2020},

date = {2020-06-01},

journal = {Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology},

volume = {50},

number = {6},

pages = {654--661},

abstract = {BACKGROUND: Mastocytosis is associated with mast cell (MC) mediator-related symptoms for which limited therapies are available. OBJECTIVE: Our aim was to assess the efficacy and safety of omalizumab in the treatment of MC mediator-related symptoms in adult patients with mastocytosis. RESULTS: We identified one multi-centre retrospective cohort study (39 patients), one retrospective cohort study (13 patients), 4 case series and 10 case reports. No published controlled randomized study was identified. We included 69 patients (13 patients with cutaneous mastocytosis and 56 with systemic mastocytosis). The mean age was 48 years. Omalizumab maintenance dose was 300 mg for the majority of patients. The mean duration of treatment was 17 months. Treatment led to a tolerability of venom immunotherapy and to a complete resolution of severe reactions in all patients with post-honeybee sting anaphylaxis. Complete resolution of idiopathic anaphylaxis episodes was noted in 84% of the patients. Complete resolution of palpitations, gastrointestinal, cutaneous, neuropsychiatric, respiratory and musculoskeletal symptoms was observed at a rate of 43%, 29%, 27%, 11%, 9% and 0%, respectively. Efficacy was maintained for the entire duration of the treatment in all but four responders. Adverse events were reported for 13 patients. CONCLUSIONS AND CLINICAL RELEVANCE: Omalizumab appears to prevent some life-threatening reactions associated with mastocytosis and may be a good option to treat the associated symptoms. However, the evidence relied upon is observational, uncontrolled and from a small number of patients. A randomized controlled trial is needed to better understand the place of omalizumab in mastocytosis treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Folkerts2020,

title = {Rapid identification of human mast cell degranulation regulators using functional genomics coupled to high-resolution confocal microscopy.},

author = {Folkerts, Jelle and Gaudenzio, Nicolas and Maurer, Marcus and Hendriks, Rudi W and Stadhouders, Ralph and Tam, See-Ying and Galli, Stephen J},

doi = {10.1038/s41596-019-0288-6},

issn = {1750-2799 (Electronic)},

year  = {2020},

date = {2020-03-01},

journal = {Nature protocols},

volume = {15},

number = {3},

pages = {1285--1310},

abstract = {Targeted functional genomics represents a powerful approach for studying gene function in vivo and in vitro. However, its application to gene expression studies in human mast cells has been hampered by low yields of human mast cell cultures and their poor transfection efficiency. We developed an imaging system in which mast cell degranulation can be visualized in single cells subjected to shRNA knockdown or CRISPR-Cas9 gene editing. By using high-resolution confocal microscopy and a fluorochrome-labeled avidin probe, one can directly assess the alteration of functional responses, i.e., degranulation, in single human mast cells (10-12 weeks old). The elimination of a drug or marker selection step avoids the use of potentially toxic treatment procedures, and the brief hands-on time of the functional analysis step enables high-throughput screening of shRNA or CRISPR-Cas9 constructs to identify genes that regulate human mast cell degranulation. The ability to analyze single cells substantially reduces the total number of cells required and enables the parallel visualization of the degranulation profiles of both edited and non-edited mast cells, offering a consistent internal control not found in other protocols. Moreover, our protocol offers a flexible choice between RNA interference (RNAi) and CRISPR-Cas9 genome editing for perturbation of gene expression using our human mast cell single-cell imaging system. Perturbation of gene expression, acquisition of microscopy data and image analysis can be completed within 5 d, requiring only standard laboratory equipment and expertise.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Meixiong2020,

title = {Nociceptor-Mast Cell Sensory Clusters as Regulators of Skin Homeostasis.},

author = {Meixiong, James and Basso, Lilian and Dong, Xinzhong and Gaudenzio, Nicolas},

doi = {10.1016/j.tins.2020.01.001},

issn = {1878-108X (Electronic)},

year  = {2020},

date = {2020-03-01},

journal = {Trends in neurosciences},

volume = {43},

number = {3},

pages = {130--132},

abstract = {Recent studies revealed the existence of unique functional links between mast cells and nociceptors in the skin. Here, we propose that mast cells and nociceptors form a single regulatory unit in both physiology and disease. In this model, MrgprB2/X2 signaling is a primary mechanism by which mast cells functionally interact with nociceptors to form specialized neuroimmune clusters that regulate pain, inflammation, and itch.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Corbiere2020,

title = {MRGPRX2 sensing of cationic compounds—A bridge between nociception and skin diseases?},

author = {Corbi{è}re, Auriane and Loste, Alexia and Gaudenzio, Nicolas},

doi = {10.1111/exd.14222},

issn = {16000625},

year  = {2020},

date = {2020-01-01},

journal = {Experimental Dermatology},

abstract = {Mast cells are innate immune cells located at many barrier sites in the body and known to protect the host against environmental threats and to be involved in allergic diseases. More recently, new studies have investigated their roles in the regulation of skin inflammation and transmission of pain and itch sensations. Mast cell signalling through the Mas-related G protein-coupled receptor (MRGPR) X2 or its mouse orthologue MRGPRB2 has been reported to be one of the major mechanism by which mast cell can regulate such processes. MRGPRX2 and MRGPRB2 can induce mast cell degranulation upon binding to a broad panel of cationic molecules such as neuropeptides, bacteria-derived quorum sensing molecules, venom peptides, host defense peptides and, unfortunately, various FDA-approved drugs. Upon activation, mast cells release granule-associated proteases, lipids and multiple cytokines that can modulate vascular permeability, immune cells recruitment and activation status of tissue-projecting nociceptive sensory neurons (ie nociceptors). Here, we discuss the modality of MRGPRX2-dependent mast cell activation and its different consequences on the patterns of skin inflammation and associated diseases. We notably emphasize how MRGPRX2-dependent skin mast cell activation might trigger various pathological traits such as pruritus, pain and inflammation and therefore become a potential therapeutic target for inflammatory pain, itch, atopic dermatitis and drugs-induced injection site reactions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Galli2020,

title = {Mast Cells in Inflammation and Disease: Recent Progress and Ongoing Concerns},

author = {Stephen J Galli and Nicolas Gaudenzio and Mindy Tsai},

url = {https://doi.org/10.1146/annurev-immunol-071719-},

doi = {10.1146/annurev-immunol-071719},

year  = {2020},

date = {2020-01-01},

journal = {Annual Review of Immunology},

volume = {5},

abstract = {Mast cells have existed long before the development of adaptive immunity, although they have been given different names. Thus, in the marine urochor-date Styela plicata, they have been designated as test cells. However, based on their morphological characteristics (including prominent cytoplasmic granules) and mediator content (including heparin, histamine, and neutral pro-teases), test cells are thought to represent members of the lineage known in vertebrates as mast cells. So this lineage presumably had important functions that preceded the development of antibodies, including IgE. Yet mast cells are best known, in humans, as key sources of mediators responsible for acute allergic reactions, notably including anaphylaxis, a severe and potentially fatal IgE-dependent immediate hypersensitivity reaction to apparently harmless antigens, including many found in foods and medicines. In this review, we briefly describe the origins of tissue mast cells and outline evidence that 49},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {The "Mast Cell and Basophil Club" of the French Society for Immunology},

author = {Arock, M. and Blank, U. and Charles, N. and Gaudenzio, N. and Georgin-Lavialle, S. and Li, M. and Ménasché, G. and Reber, L. and Vitte, J.},

year  = {2020},

date = {2020-01-01},

journal = {Eur J Immunol},

volume = {50},

number = {10},

pages = {1430-1431},

note = {Arock, Michel 

Blank, Ulrich 

Charles, Nicolas 

Gaudenzio, Nicolas 

Georgin-Lavialle, Sophie 

Li, Mei 

Ménasché, Gaël 

Reber, Laurent 

Vitte, Joana 

Germany 

Eur J Immunol. 2020 Oct;50(10):1430-1431. doi: 10.1002/eji.202070105.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Rapid identification of human mast cell degranulation regulators using functional genomics coupled to high-resolution confocal microscopy},

author = {Folkerts, J. and Gaudenzio, N. and Maurer, M. and Hendriks, R. W. and Stadhouders, R. and Tam, S. Y. and Galli, S. J.},

year  = {2020},

date = {2020-01-01},

journal = {Nat Protoc},

volume = {15},

number = {3},

pages = {1285-1310},

abstract = {Targeted functional genomics represents a powerful approach for studying gene function in vivo and in vitro. However, its application to gene expression studies in human mast cells has been hampered by low yields of human mast cell cultures and their poor transfection efficiency. We developed an imaging system in which mast cell degranulation can be visualized in single cells subjected to shRNA knockdown or CRISPR-Cas9 gene editing. By using high-resolution confocal microscopy and a fluorochrome-labeled avidin probe, one can directly assess the alteration of functional responses, i.e., degranulation, in single human mast cells (10-12 weeks old). The elimination of a drug or marker selection step avoids the use of potentially toxic treatment procedures, and the brief hands-on time of the functional analysis step enables high-throughput screening of shRNA or CRISPR-Cas9 constructs to identify genes that regulate human mast cell degranulation. The ability to analyze single cells substantially reduces the total number of cells required and enables the parallel visualization of the degranulation profiles of both edited and non-edited mast cells, offering a consistent internal control not found in other protocols. Moreover, our protocol offers a flexible choice between RNA interference (RNAi) and CRISPR-Cas9 genome editing for perturbation of gene expression using our human mast cell single-cell imaging system. Perturbation of gene expression, acquisition of microscopy data and image analysis can be completed within 5 d, requiring only standard laboratory equipment and expertise.},

note = {Folkerts, Jelle 

Gaudenzio, Nicolas 

Maurer, Marcus 

Hendriks, Rudi W 

Stadhouders, Ralph 

Tam, See-Ying 

Galli, Stephen J 

U19 AI104209/AI/NIAID NIH HHS/United States 

R01 AI132494/AI/NIAID NIH HHS/United States 

R01 AR067145/AR/NIAMS NIH HHS/United States 

Research Support, N.I.H., Extramural 

Research Support, Non-U.S. Gov't 

Nat Protoc. 2020 Mar;15(3):1285-1310. doi: 10.1038/s41596-019-0288-6. Epub 2020 Feb 14.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Mast Cells in Inflammation and Disease: Recent Progress and Ongoing Concerns},

author = {Galli, S. J. and Gaudenzio, N. and Tsai, M.},

year  = {2020},

date = {2020-01-01},

journal = {Annu Rev Immunol},

volume = {38},

pages = {49-77},

abstract = {Mast cells have existed long before the development of adaptive immunity, although they have been given different names. Thus, in the marine urochordate Styela plicata, they have been designated as test cells. However, based on their morphological characteristics (including prominent cytoplasmic granules) and mediator content (including heparin, histamine, and neutral proteases), test cells are thought to represent members of the lineage known in vertebrates as mast cells. So this lineage presumably had important functions that preceded the development of antibodies, including IgE. Yet mast cells are best known, in humans, as key sources of mediators responsible for acute allergic reactions, notably including anaphylaxis, a severe and potentially fatal IgE-dependent immediate hypersensitivity reaction to apparently harmless antigens, including many found in foods and medicines. In this review, we briefly describe the origins of tissue mast cells and outline evidence that these cells can have beneficial as well as detrimental functions, both innately and as participants in adaptive immune responses. We also discuss aspects of mast cell heterogeneity and comment on how the plasticity of this lineage may provide insight into its roles in health and disease. Finally, we consider some currently open questions that are yet unresolved.},

note = {Galli, Stephen J 

Gaudenzio, Nicolas 

Tsai, Mindy 

U19 AI104209/AI/NIAID NIH HHS/United States 

R01 AR067145/AR/NIAMS NIH HHS/United States 

Research Support, N.I.H., Extramural 

Research Support, Non-U.S. Gov't 

United States 

Annu Rev Immunol. 2020 Apr 26;38:49-77. doi: 10.1146/annurev-immunol-071719-094903.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Omalizumab in the treatment of adult patients with mastocytosis: A systematic review},

author = {Jendoubi, F. and Gaudenzio, N. and Gallini, A. and Negretto, M. and Paul, C. and Bulai Livideanu, C.},

year  = {2020},

date = {2020-01-01},

journal = {Clin Exp Allergy},

volume = {50},

number = {6},

pages = {654-661},

abstract = {BACKGROUND: Mastocytosis is associated with mast cell (MC) mediator-related symptoms for which limited therapies are available. OBJECTIVE: Our aim was to assess the efficacy and safety of omalizumab in the treatment of MC mediator-related symptoms in adult patients with mastocytosis. RESULTS: We identified one multi-centre retrospective cohort study (39 patients), one retrospective cohort study (13 patients), 4 case series and 10 case reports. No published controlled randomized study was identified. We included 69 patients (13 patients with cutaneous mastocytosis and 56 with systemic mastocytosis). The mean age was 48 years. Omalizumab maintenance dose was 300 mg for the majority of patients. The mean duration of treatment was 17 months. Treatment led to a tolerability of venom immunotherapy and to a complete resolution of severe reactions in all patients with post-honeybee sting anaphylaxis. Complete resolution of idiopathic anaphylaxis episodes was noted in 84% of the patients. Complete resolution of palpitations, gastrointestinal, cutaneous, neuropsychiatric, respiratory and musculoskeletal symptoms was observed at a rate of 43%, 29%, 27%, 11%, 9% and 0%, respectively. Efficacy was maintained for the entire duration of the treatment in all but four responders. Adverse events were reported for 13 patients. CONCLUSIONS AND CLINICAL RELEVANCE: Omalizumab appears to prevent some life-threatening reactions associated with mastocytosis and may be a good option to treat the associated symptoms. However, the evidence relied upon is observational, uncontrolled and from a small number of patients. A randomized controlled trial is needed to better understand the place of omalizumab in mastocytosis treatment.},

note = {Jendoubi, Fatma 

Gaudenzio, Nicolas 

Gallini, Adeline 

Negretto, Mathilde 

Paul, Carle 

Bulai Livideanu, Cristina 

England 

Clin Exp Allergy. 2020 Jun;50(6):654-661. doi: 10.1111/cea.13592. Epub 2020 Mar 25.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Nociceptor-Mast Cell Sensory Clusters as Regulators of Skin Homeostasis},

author = {Meixiong, J. and Basso, L. and Dong, X. and Gaudenzio, N.},

year  = {2020},

date = {2020-01-01},

journal = {Trends Neurosci},

volume = {43},

number = {3},

pages = {130-132},

abstract = {Recent studies revealed the existence of unique functional links between mast cells and nociceptors in the skin. Here, we propose that mast cells and nociceptors form a single regulatory unit in both physiology and disease. In this model, MrgprB2/X2 signaling is a primary mechanism by which mast cells functionally interact with nociceptors to form specialized neuroimmune clusters that regulate pain, inflammation, and itch.},

note = {Meixiong, James 

Basso, Lilian 

Dong, Xinzhong 

Gaudenzio, Nicolas 

Research Support, N.I.H., Extramural 

Research Support, Non-U.S. Gov't 

England 

Trends Neurosci. 2020 Mar;43(3):130-132. doi: 10.1016/j.tins.2020.01.001. Epub 2020 Jan 31.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {IgE Effector Mechanisms, in Concert with Mast Cells, Contribute to Acquired Host Defense against Staphylococcusaureus},

author = {Starkl, P. and Watzenboeck, M. L. and Popov, L. M. and Zahalka, S. and Hladik, A. and Lakovits, K. and Radhouani, M. and Haschemi, A. and Marichal, T. and Reber, L. L. and Gaudenzio, N. and Sibilano, R. and Stulik, L. and Fontaine, F. and Mueller, A. C. and Amieva, M. R. and Galli, S. J. and Knapp, S.},

year  = {2020},

date = {2020-01-01},

journal = {Immunity},

volume = {53},

number = {4},

pages = {793-804 e9},

abstract = {Allergies are considered to represent mal-directed type 2 immune responses against mostly innocuous exogenous compounds. Immunoglobulin E (IgE) antibodies are a characteristic feature of allergies and mediate hypersensitivity against allergens through activation of effector cells, particularly mast cells (MCs). Although the physiological functions of this dangerous branch of immunity have remained enigmatic, recent evidence shows that allergic immune reactions can help to protect against the toxicity of venoms. Because bacteria are a potent alternative source of toxins, we assessed the possible role of allergy-like type 2 immunity in antibacterial host defense. We discovered that the adaptive immune response against Staphylococcus aureus (SA) skin infection substantially improved systemic host defense against secondary SA infections in mice. Moreover, this acquired protection depended on IgE effector mechanisms and MCs. Importantly, our results reveal a previously unknown physiological function of allergic immune responses, IgE antibodies, and MCs in host defense against a pathogenic bacterium.},

note = {Starkl, Philipp 

Watzenboeck, Martin L 

Popov, Lauren M 

Zahalka, Sophie 

Hladik, Anastasiya 

Lakovits, Karin 

Radhouani, Mariem 

Haschemi, Arvand 

Marichal, Thomas 

Reber, Laurent L 

Gaudenzio, Nicolas 

Sibilano, Riccardo 

Stulik, Lukas 

Fontaine, Frédéric 

Mueller, André C 

Amieva, Manuel R 

Galli, Stephen J 

Knapp, Sylvia 

R01 AI023990/AI/NIAID NIH HHS/United States 

R01 AI070813/AI/NIAID NIH HHS/United States 

R01 AI132494/AI/NIAID NIH HHS/United States 

R01 AR067145/AR/NIAMS NIH HHS/United States 

Research Support, N.I.H., Extramural 

Research Support, Non-U.S. Gov't 

Immunity. 2020 Oct 13;53(4):793-804.e9. doi: 10.1016/j.immuni.2020.08.002. Epub 2020 Sep 9.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Basso2019,

title = {Peripheral neurons: Master regulators of skin and mucosal immune response.},

author = {Basso, Lilian and Serhan, Nadine and Tauber, Marie and Gaudenzio, Nicolas},

doi = {10.1002/eji.201848027},

issn = {1521-4141 (Electronic)},

year  = {2019},

date = {2019-11-01},

journal = {European journal of immunology},

volume = {49},

number = {11},

pages = {1984--1997},

abstract = {The body is innervated by a meshwork of heterogeneous peripheral neurons (including sensory neurons) which project virtually to all the organs. Peripheral neurons have been studied extensively in the context of their primary function of initiation of voluntary and involuntary movement, transmission of sensations and induction of appropriate behavioral response such as withdrawal to avoid tissue injury or scratching to remove irritating molecules. More recently, breakthrough articles have shown that, on top of their primary function of signal transmission to the spinal cord and brain, peripheral neurons (including afferent neurons) could directly sense environmental alarms and consequently regulate the development of various type of immune responses through the release of neuropeptides or growth factors. In this review, we discuss recent advances in the neural regulation of the immune response, both in physiological and pathological contexts by taking into account the type of organs (lungs, skin and gut), subtypes of peripheral neurons (sympathetic, nociceptive and intrinsic gut neurons) or immune cells and strains of pathogens studied. We also highlight future challenges in the field and potential therapeutic innovations targeting neuro-immune interactions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pundir2019,

title = {A Connective Tissue Mast-Cell-Specific Receptor Detects Bacterial Quorum-Sensing Molecules and Mediates Antibacterial Immunity.},

author = {Pundir, Priyanka and Liu, Rui and Vasavda, Chirag and Serhan, Nadine and Limjunyawong, Nathachit and Yee, Rebecca and Zhan, Yingzhuan and Dong, Xintong and Wu, Xueqing and Zhang, Ying and Snyder, Solomon H and Gaudenzio, Nicolas and Vidal, Jorge E and Dong, Xinzhong},

doi = {10.1016/j.chom.2019.06.003},

issn = {1934-6069 (Electronic)},

year  = {2019},

date = {2019-07-01},

journal = {Cell host & microbe},

volume = {26},

number = {1},

pages = {114--122.e8},

abstract = {Quorum-sensing molecules (QSMs) are secreted by bacteria to signal population density. Upon reaching a critical concentration, QSMs induce transcriptional alterations in bacteria, which enable virulence factor expression and biofilm formation. It is unclear whether mammalian hosts can recognize QSMs to trigger responsive antibacterial immunity. We report that mouse mast-cell-specific G-protein-coupled receptor Mrgprb2 and its human homolog MRGPRX2 are receptors for Gram-positive QSMs, including competence-stimulating peptide (CSP)-1. CSP-1 activates Mrgprb2 and MRGPRX2, triggering mast cell degranulation, which inhibits bacterial growth and prevents biofilm formation. Such antibacterial functions are reduced in Mrgprb2-deficient mast cells, while wild-type mast cells fail to inhibit the growth of bacterial strains lacking CSP-1. Mrgprb2-knockout mice exhibit reduced bacterial clearance, while pharmacologically activating Mrgprb2 in vivo eliminates bacteria and improves disease score. These findings identify a host defense mechanism that uses QSMs as an "Achilles heel" and suggest MRGPRX2 as a potential therapeutic target for controlling bacterial infections.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Serhan2019,

title = {House dust mites activate nociceptor–mast cell clusters to drive type 2 skin inflammation},

author = {Serhan, Nadine and Basso, Lilian and Sibilano, Riccardo and Petitfils, Camille and Meixiong, James and Bonnart, Chrystelle and Reber, Laurent L. and Marichal, Thomas and Starkl, Philipp and Cenac, Nicolas and Dong, Xinzhong and Tsai, Mindy and Galli, Stephen J. and Gaudenzio, Nicolas},

doi = {10.1038/s41590-019-0493-z},

issn = {15292916},

year  = {2019},

date = {2019-01-01},

journal = {Nature Immunology},

abstract = {Allergic skin diseases, such as atopic dermatitis, are clinically characterized by severe itching and type 2 immunity-associated hypersensitivity to widely distributed allergens, including those derived from house dust mites (HDMs). Here we found that HDMs with cysteine protease activity directly activated peptidergic nociceptors, which are neuropeptide-producing nociceptive sensory neurons that express the ion channel TRPV1 and Tac1, the gene encoding the precursor for the neuropeptide substance P. Intravital imaging and genetic approaches indicated that HDM-activated nociceptors drive the development of allergic skin inflammation by inducing the degranulation of mast cells contiguous to such nociceptors, through the release of substance P and the activation of the cationic molecule receptor MRGPRB2 on mast cells. These data indicate that, after exposure to HDM allergens, activation of TRPV1+Tac1+ nociceptor–MRGPRB2+ mast cell sensory clusters represents a key early event in the development of allergic skin reactions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Peripheral neurons: Master regulators of skin and mucosal immune response},

author = {Basso, L. and Serhan, N. and Tauber, M. and Gaudenzio, N.},

year  = {2019},

date = {2019-01-01},

journal = {Eur J Immunol},

volume = {49},

number = {11},

pages = {1984-1997},

abstract = {The body is innervated by a meshwork of heterogeneous peripheral neurons (including sensory neurons) which project virtually to all the organs. Peripheral neurons have been studied extensively in the context of their primary function of initiation of voluntary and involuntary movement, transmission of sensations and induction of appropriate behavioral response such as withdrawal to avoid tissue injury or scratching to remove irritating molecules. More recently, breakthrough articles have shown that, on top of their primary function of signal transmission to the spinal cord and brain, peripheral neurons (including afferent neurons) could directly sense environmental alarms and consequently regulate the development of various type of immune responses through the release of neuropeptides or growth factors. In this review, we discuss recent advances in the neural regulation of the immune response, both in physiological and pathological contexts by taking into account the type of organs (lungs, skin and gut), subtypes of peripheral neurons (sympathetic, nociceptive and intrinsic gut neurons) or immune cells and strains of pathogens studied. We also highlight future challenges in the field and potential therapeutic innovations targeting neuro-immune interactions.},

note = {Basso, Lilian 

Serhan, Nadine 

Tauber, Marie 

Gaudenzio, Nicolas 

Société Française d'Allergologie/International 

ERC-2018-STG #802041/H2020 European Research Council/International 

Société Française de Dermatologie et de Pathologie Sexuellement Transmissible/International 

Institut National de la Santé et de la Recherche Médicale/International 

Individual Fellowship H2020-MSCA-IF-2016 749629/H2020 Marie Skłodowska-Curie Actions/International 

Research Support, Non-U.S. Gov't 

Review 

Germany 

Eur J Immunol. 2019 Nov;49(11):1984-1997. doi: 10.1002/eji.201848027. Epub 2019 Aug 7.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {House dust mites activate nociceptor-mast cell clusters to drive type 2 skin inflammation},

author = {Serhan, N. and Basso, L. and Sibilano, R. and Petitfils, C. and Meixiong, J. and Bonnart, C. and Reber, L. L. and Marichal, T. and Starkl, P. and Cenac, N. and Dong, X. and Tsai, M. and Galli, S. J. and Gaudenzio, N.},

year  = {2019},

date = {2019-01-01},

journal = {Nat Immunol},

volume = {20},

number = {11},

pages = {1435-1443},

abstract = {Allergic skin diseases, such as atopic dermatitis, are clinically characterized by severe itching and type 2 immunity-associated hypersensitivity to widely distributed allergens, including those derived from house dust mites (HDMs). Here we found that HDMs with cysteine protease activity directly activated peptidergic nociceptors, which are neuropeptide-producing nociceptive sensory neurons that express the ion channel TRPV1 and Tac1, the gene encoding the precursor for the neuropeptide substance P. Intravital imaging and genetic approaches indicated that HDM-activated nociceptors drive the development of allergic skin inflammation by inducing the degranulation of mast cells contiguous to such nociceptors, through the release of substance P and the activation of the cationic molecule receptor MRGPRB2 on mast cells. These data indicate that, after exposure to HDM allergens, activation of TRPV1(+)Tac1(+) nociceptor-MRGPRB2(+) mast cell sensory clusters represents a key early event in the development of allergic skin reactions.},

note = {Serhan, Nadine 

Basso, Lilian 

Sibilano, Riccardo 

Petitfils, Camille 

Meixiong, James 

Bonnart, Chrystelle 

Reber, Laurent L 

Marichal, Thomas 

Starkl, Philipp 

Cenac, Nicolas 

Dong, Xinzhong 

Tsai, Mindy 

Galli, Stephen J 

Gaudenzio, Nicolas 

U19 AI104209/AI/NIAID NIH HHS/United States 

P30 NS069375/NS/NINDS NIH HHS/United States 

R01 AI132494/AI/NIAID NIH HHS/United States 

R01 AR067145/AR/NIAMS NIH HHS/United States 

802041/ERC_/European Research Council/International 

Research Support, N.I.H., Extramural 

Research Support, Non-U.S. Gov't 

Nat Immunol. 2019 Nov;20(11):1435-1443. doi: 10.1038/s41590-019-0493-z. Epub 2019 Oct 7.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gaudenzio2018,

title = {Genetic and Imaging Approaches Reveal Pro-Inflammatory and Immunoregulatory Roles of Mast Cells in Contact Hypersensitivity.},

author = {Gaudenzio, Nicolas and Marichal, Thomas and Galli, Stephen J and Reber, Laurent L},

doi = {10.3389/fimmu.2018.01275},

issn = {1664-3224 (Print)},

year  = {2018},

date = {2018-01-01},

journal = {Frontiers in immunology},

volume = {9},

pages = {1275},

abstract = {Contact hypersensitivity (CHS) is a common T cell-mediated skin disease induced by epicutaneous sensitization to haptens. Mast cells (MCs) are widely deployed in the skin and can be activated during CHS responses to secrete diverse products, including some with pro-inflammatory and anti-inflammatory functions. Conflicting results have been obtained regarding pathogenic versus protective roles of MCs in CHS, and this has been attributed in part to the limitations of certain models for studying MC functions in vivo. This review discusses recent advances in the development and analysis of mouse models to investigate the roles of MCs and MC-associated products in vivo. Notably, fluorescent avidin-based two-photon imaging approaches enable in vivo selective labeling and simultaneous tracking of MC secretory granules (e.g., during MC degranulation) and MC gene activation by real-time longitudinal intravital microscopy in living mice. The combination of such genetic and imaging tools has shed new light on the controversial role played by MCs in mouse models of CHS. On the one hand, they can amplify CHS responses of mild severity while, on the other hand, can limit the inflammation and tissue injury associated with more severe or chronic models, in part by representing an initial source of the anti-inflammatory cytokine IL-10.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Human mast cells as antigen-presenting cells: When is this role important in vivo?},

author = {Galli, S. J. and Gaudenzio, N.},

year  = {2018},

date = {2018-01-01},

journal = {J Allergy Clin Immunol},

volume = {141},

number = {1},

pages = {92-93},

note = {Galli, Stephen J 

Gaudenzio, Nicolas 

Comment 

Editorial 

United States 

J Allergy Clin Immunol. 2018 Jan;141(1):92-93. doi: 10.1016/j.jaci.2017.05.029. Epub 2017 Jun 15.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Genetic and Imaging Approaches Reveal Pro-Inflammatory and Immunoregulatory Roles of Mast Cells in Contact Hypersensitivity},

author = {Gaudenzio, N. and Marichal, T. and Galli, S. J. and Reber, L. L.},

year  = {2018},

date = {2018-01-01},

journal = {Front Immunol},

volume = {9},

pages = {1275},

abstract = {Contact hypersensitivity (CHS) is a common T cell-mediated skin disease induced by epicutaneous sensitization to haptens. Mast cells (MCs) are widely deployed in the skin and can be activated during CHS responses to secrete diverse products, including some with pro-inflammatory and anti-inflammatory functions. Conflicting results have been obtained regarding pathogenic versus protective roles of MCs in CHS, and this has been attributed in part to the limitations of certain models for studying MC functions in vivo. This review discusses recent advances in the development and analysis of mouse models to investigate the roles of MCs and MC-associated products in vivo. Notably, fluorescent avidin-based two-photon imaging approaches enable in vivo selective labeling and simultaneous tracking of MC secretory granules (e.g., during MC degranulation) and MC gene activation by real-time longitudinal intravital microscopy in living mice. The combination of such genetic and imaging tools has shed new light on the controversial role played by MCs in mouse models of CHS. On the one hand, they can amplify CHS responses of mild severity while, on the other hand, can limit the inflammation and tissue injury associated with more severe or chronic models, in part by representing an initial source of the anti-inflammatory cytokine IL-10.},

note = {Gaudenzio, Nicolas 

Marichal, Thomas 

Galli, Stephen J 

Reber, Laurent L 

R01 AI132494/AI/NIAID NIH HHS/United States 

R01 AR067145/AR/NIAMS NIH HHS/United States 

Research Support, N.I.H., Extramural 

Research Support, Non-U.S. Gov't 

Research Support, U.S. Gov't, Non-P.H.S. 

Review 

Front Immunol. 2018 Jun 5;9:1275. doi: 10.3389/fimmu.2018.01275. eCollection 2018.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Reber2017,

title = {Imaging protective mast cells in living mice during severe contact hypersensitivity.},

author = {Reber, Laurent L and Sibilano, Riccardo and Starkl, Philipp and Roers, Axel and Grimbaldeston, Michele A and Tsai, Mindy and Gaudenzio, Nicolas and Galli, Stephen J},

doi = {10.1172/jci.insight.92900},

issn = {2379-3708 (Electronic)},

year  = {2017},

date = {2017-05-01},

journal = {JCI insight},

volume = {2},

number = {9},

abstract = {Contact hypersensitivity (CHS) is a common skin disease induced by epicutaneous sensitization to haptens. Conflicting results have been obtained regarding pathogenic versus protective roles of mast cells (MCs) in CHS, and this has been attributed in part to the limitations of certain models for studying MC functions in vivo. Here we describe a fluorescent imaging approach that enables in vivo selective labeling and tracking of MC secretory granules by real-time intravital 2-photon microscopy in living mice, and permits the identification of such MCs as a potential source of cytokines in different disease models. We show using this method that dermal MCs release their granules progressively into the surrounding microenvironment, but also represent an initial source of the antiinflammatory cytokine IL-10, during the early phase of severe CHS reactions. Finally, using 3 different types of MC-deficient mice, as well as mice in which IL-10 is ablated specifically in MCs, we show that IL-10 production by MCs can significantly limit the inflammation and tissue pathology observed in severe CHS reactions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Reber2017b,

title = {Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide.},

author = {Reber, Laurent L and Gillis, Caitlin M and Starkl, Philipp and J{ö}nsson, Friederike and Sibilano, Riccardo and Marichal, Thomas and Gaudenzio, Nicolas and B{é}rard, Marion and Rogalla, Stephan and Contag, Christopher H and Bruhns, Pierre and Galli, Stephen J},

doi = {10.1084/jem.20161238},

issn = {1540-9538 (Electronic)},

year  = {2017},

date = {2017-05-01},

journal = {The Journal of experimental medicine},

volume = {214},

number = {5},

pages = {1249--1258},

abstract = {Neutrophils have crucial antimicrobial functions but are also thought to contribute to tissue injury upon exposure to bacterial products, such as lipopolysaccharide (LPS). To study the role of neutrophils in LPS-induced endotoxemia, we developed a new mouse model, PMN(DTR) mice, in which injection of diphtheria toxin induces selective neutrophil ablation. Using this model, we found, surprisingly, that neutrophils serve to protect the host from LPS-induced lethal inflammation. This protective role was observed in conventional and germ-free animal facilities, indicating that it does not depend on a particular microbiological environment. Blockade or genetic deletion of myeloperoxidase (MPO), a key neutrophil enzyme, significantly increased mortality after LPS challenge, and adoptive transfer experiments confirmed that neutrophil-derived MPO contributes importantly to protection from endotoxemia. Our findings imply that, in addition to their well-established antimicrobial properties, neutrophils can contribute to optimal host protection by limiting the extent of endotoxin-induced inflammation in an MPO-dependent manner.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ho2017,

title = {Decoupling the Functional Pleiotropy of Stem Cell Factor by Tuning c-Kit Signaling.},

author = {Ho, Chia Chi M and Chhabra, Akanksha and Starkl, Philipp and Schnorr, Peter-John and Wilmes, Stephan and Moraga, Ignacio and Kwon, Hye-Sook and Gaudenzio, Nicolas and Sibilano, Riccardo and Wehrman, Tom S and Gakovic, Milica and Sockolosky, Jonathan T and Tiffany, Matthew R and Ring, Aaron M and Piehler, Jacob and Weissman, Irving L and Galli, Stephen J and Shizuru, Judith A and Garcia, K Christopher},

doi = {10.1016/j.cell.2017.02.011},

issn = {1097-4172 (Electronic)},

year  = {2017},

date = {2017-03-01},

journal = {Cell},

volume = {168},

number = {6},

pages = {1041--1052.e18},

abstract = {Most secreted growth factors and cytokines are functionally pleiotropic because their receptors are expressed on diverse cell types. While important for normal mammalian physiology, pleiotropy limits the efficacy of cytokines and growth factors as therapeutics. Stem cell factor (SCF) is a growth factor that acts through the c-Kit receptor tyrosine kinase to elicit hematopoietic progenitor expansion but can be toxic when administered in vivo because it concurrently activates mast cells. We engineered a mechanism-based SCF partial agonist that impaired c-Kit dimerization, truncating downstream signaling amplitude. This SCF variant elicited biased activation of hematopoietic progenitors over mast cells in vitro and in vivo. Mouse models of SCF-mediated anaphylaxis, radioprotection, and hematopoietic expansion revealed that this SCF partial agonist retained therapeutic efficacy while exhibiting virtually no anaphylactic off-target effects. The approach of biasing cell activation by tuning signaling thresholds and outputs has applications to many dimeric receptor-ligand systems.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mukai2017,

title = {Assessing basophil activation by using flow cytometry and mass cytometry in blood stored 24 hours before analysis.},

author = {Mukai, Kaori and Gaudenzio, Nicolas and Gupta, Sheena and Vivanco, Nora and Bendall, Sean C and Maecker, Holden T and Chinthrajah, Rebecca S and Tsai, Mindy and Nadeau, Kari C and Galli, Stephen J},

doi = {10.1016/j.jaci.2016.04.060},

issn = {1097-6825 (Electronic)},

year  = {2017},

date = {2017-03-01},

journal = {The Journal of allergy and clinical immunology},

volume = {139},

number = {3},

pages = {889--899.e11},

abstract = {BACKGROUND: Basophil activation tests (BATs) have promise for research and for clinical monitoring of patients with allergies. However, BAT protocols vary in blood anticoagulant used and temperature and time of storage before testing, complicating comparisons of results from various studies. OBJECTIVE: We attempted to establish a BAT protocol that would permit analysis of blood within 24 hours of obtaining the sample. METHODS: Blood from 46 healthy donors and 120 patients with peanut allergy was collected into EDTA or heparin tubes, and samples were stored at 4°C or room temperature for 4 or 24 hours before performing BATs. RESULTS: Stimulation with anti-IgE or IL-3 resulted in strong upregulation of basophil CD203c in samples collected in EDTA or heparin, stored at 4°C, and analyzed 24 hours after sample collection. However, a CD63(hi) population of basophils was not observed in any conditions in EDTA-treated samples unless exogenous calcium/magnesium was added at the time of anti-IgE stimulation. By contrast, blood samples collected in heparin tubes were adequate for quantification of upregulation of basophil CD203c and identification of a population of CD63(hi) basophils, irrespective of whether the specimens were analyzed by means of conventional flow cytometry or cytometry by time-of-flight mass spectrometry, and such tests could be performed after blood was stored for 24 hours at 4°C. CONCLUSION: BATs to measure upregulation of basophil CD203c and induction of a CD63(hi) basophil population can be conducted with blood obtained in heparin tubes and stored at 4°C for 24 hours.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Balbino2017,

title = {Pathways of immediate hypothermia and leukocyte infiltration in an adjuvant-free mouse model of anaphylaxis.},

author = {Balbino, Bianca and Sibilano, Riccardo and Starkl, Philipp and Marichal, Thomas and Gaudenzio, Nicolas and Karasuyama, Hajime and Bruhns, Pierre and Tsai, Mindy and Reber, Laurent L and Galli, Stephen J},

doi = {10.1016/j.jaci.2016.05.047},

issn = {1097-6825 (Electronic)},

year  = {2017},

date = {2017-02-01},

journal = {The Journal of allergy and clinical immunology},

volume = {139},

number = {2},

pages = {584--596.e10},

abstract = {BACKGROUND: Conflicting results have been obtained regarding the roles of Fc receptors and effector cells in models of active systemic anaphylaxis (ASA). In part, this might reflect the choice of adjuvant used during sensitization because various adjuvants might differentially influence the production of particular antibody isotypes. OBJECTIVE: We developed an "adjuvant-free" mouse model of ASA and assessed the contributions of components of the "classical" and "alternative" pathways in this model. METHODS: Mice were sensitized intraperitoneally with ovalbumin at weekly intervals for 6 weeks and challenged intraperitoneally with ovalbumin 2 weeks later. RESULTS: Wild-type animals had immediate hypothermia and late-phase intraperitoneal inflammation in this model. These features were reduced in mice lacking the IgE receptor Fc$epsilon$RI, the IgG receptor Fc$gamma$RIII or the common $gamma$-chain FcR$gamma$. Fc$gamma$RIV blockade resulted in a partial reduction of inflammation without any effect on hypothermia. Depletion of monocytes/macrophages with clodronate liposomes significantly reduced the hypothermia response. By contrast, depletion of neutrophils or basophils had no significant effects in this ASA model. Both the hypothermia and inflammation were dependent on platelet-activating factor and histamine and were reduced in 2 types of mast cell (MC)-deficient mice. Finally, engraftment of MC-deficient mice with bone marrow-derived cultured MCs significantly exacerbated the hypothermia response and restored inflammation to levels similar to those observed in wild-type mice. CONCLUSION: Components of the classical and alternative pathways contribute to anaphylaxis in this adjuvant-free model, with key roles for MCs and monocytes/macrophages.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Pathways of immediate hypothermia and leukocyte infiltration in an adjuvant-free mouse model of anaphylaxis},

author = {Balbino, B. and Sibilano, R. and Starkl, P. and Marichal, T. and Gaudenzio, N. and Karasuyama, H. and Bruhns, P. and Tsai, M. and Reber, L. L. and Galli, S. J.},

year  = {2017},

date = {2017-01-01},

journal = {J Allergy Clin Immunol},

volume = {139},

number = {2},

pages = {584-596 e10},

abstract = {BACKGROUND: Conflicting results have been obtained regarding the roles of Fc receptors and effector cells in models of active systemic anaphylaxis (ASA). In part, this might reflect the choice of adjuvant used during sensitization because various adjuvants might differentially influence the production of particular antibody isotypes. OBJECTIVE: We developed an "adjuvant-free" mouse model of ASA and assessed the contributions of components of the "classical" and "alternative" pathways in this model. METHODS: Mice were sensitized intraperitoneally with ovalbumin at weekly intervals for 6 weeks and challenged intraperitoneally with ovalbumin 2 weeks later. RESULTS: Wild-type animals had immediate hypothermia and late-phase intraperitoneal inflammation in this model. These features were reduced in mice lacking the IgE receptor FcεRI, the IgG receptor FcγRIII or the common γ-chain FcRγ. FcγRIV blockade resulted in a partial reduction of inflammation without any effect on hypothermia. Depletion of monocytes/macrophages with clodronate liposomes significantly reduced the hypothermia response. By contrast, depletion of neutrophils or basophils had no significant effects in this ASA model. Both the hypothermia and inflammation were dependent on platelet-activating factor and histamine and were reduced in 2 types of mast cell (MC)-deficient mice. Finally, engraftment of MC-deficient mice with bone marrow-derived cultured MCs significantly exacerbated the hypothermia response and restored inflammation to levels similar to those observed in wild-type mice. CONCLUSION: Components of the classical and alternative pathways contribute to anaphylaxis in this adjuvant-free model, with key roles for MCs and monocytes/macrophages.},

note = {Balbino, Bianca 

Sibilano, Riccardo 

Starkl, Philipp 

Marichal, Thomas 

Gaudenzio, Nicolas 

Karasuyama, Hajime 

Bruhns, Pierre 

Tsai, Mindy 

Reber, Laurent L 

Galli, Stephen J 

U19 AI104209/AI/NIAID NIH HHS/United States 

R01 AI023990/AI/NIAID NIH HHS/United States 

R01 AR067145/AR/NIAMS NIH HHS/United States 

R01 CA072074/CA/NCI NIH HHS/United States 

R01 AI070813/AI/NIAID NIH HHS/United States 

UL1 RR025744/RR/NCRR NIH HHS/United States 

K99 AI110645/AI/NIAID NIH HHS/United States 

Research Support, N.I.H., Extramural 

Research Support, Non-U.S. Gov't 

J Allergy Clin Immunol. 2017 Feb;139(2):584-596.e10. doi: 10.1016/j.jaci.2016.05.047. Epub 2016 Jul 17.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Decoupling the Functional Pleiotropy of Stem Cell Factor by Tuning c-Kit Signaling},

author = {Ho, C. C. M. and Chhabra, A. and Starkl, P. and Schnorr, P. J. and Wilmes, S. and Moraga, I. and Kwon, H. S. and Gaudenzio, N. and Sibilano, R. and Wehrman, T. S. and Gakovic, M. and Sockolosky, J. T. and Tiffany, M. R. and Ring, A. M. and Piehler, J. and Weissman, I. L. and Galli, S. J. and Shizuru, J. A. and Garcia, K. C.},

year  = {2017},

date = {2017-01-01},

journal = {Cell},

volume = {168},

number = {6},

pages = {1041-1052 e18},

abstract = {Most secreted growth factors and cytokines are functionally pleiotropic because their receptors are expressed on diverse cell types. While important for normal mammalian physiology, pleiotropy limits the efficacy of cytokines and growth factors as therapeutics. Stem cell factor (SCF) is a growth factor that acts through the c-Kit receptor tyrosine kinase to elicit hematopoietic progenitor expansion but can be toxic when administered in vivo because it concurrently activates mast cells. We engineered a mechanism-based SCF partial agonist that impaired c-Kit dimerization, truncating downstream signaling amplitude. This SCF variant elicited biased activation of hematopoietic progenitors over mast cells in vitro and in vivo. Mouse models of SCF-mediated anaphylaxis, radioprotection, and hematopoietic expansion revealed that this SCF partial agonist retained therapeutic efficacy while exhibiting virtually no anaphylactic off-target effects. The approach of biasing cell activation by tuning signaling thresholds and outputs has applications to many dimeric receptor-ligand systems.},

note = {Ho, Chia Chi M 

Chhabra, Akanksha 

Starkl, Philipp 

Schnorr, Peter-John 

Wilmes, Stephan 

Moraga, Ignacio 

Kwon, Hye-Sook 

Gaudenzio, Nicolas 

Sibilano, Riccardo 

Wehrman, Tom S 

Gakovic, Milica 

Sockolosky, Jonathan T 

Tiffany, Matthew R 

Ring, Aaron M 

Piehler, Jacob 

Weissman, Irving L 

Galli, Stephen J 

Shizuru, Judith A 

Garcia, K Christopher 

R01 CA177684/CA/NCI NIH HHS/United States 

R37 AI051321/AI/NIAID NIH HHS/United States 

R43 AI072905/AI/NIAID NIH HHS/United States 

HHMI/Howard Hughes Medical Institute/United States 

Research Support, N.I.H., Extramural 

Research Support, Non-U.S. Gov't 

Cell. 2017 Mar 9;168(6):1041-1052.e18. doi: 10.1016/j.cell.2017.02.011.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Assessing basophil activation by using flow cytometry and mass cytometry in blood stored 24 hours before analysis},

author = {Mukai, K. and Gaudenzio, N. and Gupta, S. and Vivanco, N. and Bendall, S. C. and Maecker, H. T. and Chinthrajah, R. S. and Tsai, M. and Nadeau, K. C. and Galli, S. J.},

year  = {2017},

date = {2017-01-01},

journal = {J Allergy Clin Immunol},

volume = {139},

number = {3},

pages = {889-899 e11},

abstract = {BACKGROUND: Basophil activation tests (BATs) have promise for research and for clinical monitoring of patients with allergies. However, BAT protocols vary in blood anticoagulant used and temperature and time of storage before testing, complicating comparisons of results from various studies. OBJECTIVE: We attempted to establish a BAT protocol that would permit analysis of blood within 24 hours of obtaining the sample. METHODS: Blood from 46 healthy donors and 120 patients with peanut allergy was collected into EDTA or heparin tubes, and samples were stored at 4°C or room temperature for 4 or 24 hours before performing BATs. RESULTS: Stimulation with anti-IgE or IL-3 resulted in strong upregulation of basophil CD203c in samples collected in EDTA or heparin, stored at 4°C, and analyzed 24 hours after sample collection. However, a CD63(hi) population of basophils was not observed in any conditions in EDTA-treated samples unless exogenous calcium/magnesium was added at the time of anti-IgE stimulation. By contrast, blood samples collected in heparin tubes were adequate for quantification of upregulation of basophil CD203c and identification of a population of CD63(hi) basophils, irrespective of whether the specimens were analyzed by means of conventional flow cytometry or cytometry by time-of-flight mass spectrometry, and such tests could be performed after blood was stored for 24 hours at 4°C. CONCLUSION: BATs to measure upregulation of basophil CD203c and induction of a CD63(hi) basophil population can be conducted with blood obtained in heparin tubes and stored at 4°C for 24 hours.},

note = {Mukai, Kaori 

Gaudenzio, Nicolas 

Gupta, Sheena 

Vivanco, Nora 

Bendall, Sean C 

Maecker, Holden T 

Chinthrajah, Rebecca S 

Tsai, Mindy 

Nadeau, Kari C 

Galli, Stephen J 

U19 AI104209/AI/NIAID NIH HHS/United States 

J Allergy Clin Immunol. 2017 Mar;139(3):889-899.e11. doi: 10.1016/j.jaci.2016.04.060. Epub 2016 Jul 15.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide},

author = {Reber, L. L. and Gillis, C. M. and Starkl, P. and Jönsson, F. and Sibilano, R. and Marichal, T. and Gaudenzio, N. and Bérard, M. and Rogalla, S. and Contag, C. H. and Bruhns, P. and Galli, S. J.},

year  = {2017},

date = {2017-01-01},

journal = {J Exp Med},

volume = {214},

number = {5},

pages = {1249-1258},

abstract = {Neutrophils have crucial antimicrobial functions but are also thought to contribute to tissue injury upon exposure to bacterial products, such as lipopolysaccharide (LPS). To study the role of neutrophils in LPS-induced endotoxemia, we developed a new mouse model, PMN(DTR) mice, in which injection of diphtheria toxin induces selective neutrophil ablation. Using this model, we found, surprisingly, that neutrophils serve to protect the host from LPS-induced lethal inflammation. This protective role was observed in conventional and germ-free animal facilities, indicating that it does not depend on a particular microbiological environment. Blockade or genetic deletion of myeloperoxidase (MPO), a key neutrophil enzyme, significantly increased mortality after LPS challenge, and adoptive transfer experiments confirmed that neutrophil-derived MPO contributes importantly to protection from endotoxemia. Our findings imply that, in addition to their well-established antimicrobial properties, neutrophils can contribute to optimal host protection by limiting the extent of endotoxin-induced inflammation in an MPO-dependent manner.},

note = {Reber, Laurent L 

Gillis, Caitlin M 

Starkl, Philipp 

Jönsson, Friederike 

Sibilano, Riccardo 

Marichal, Thomas 

Gaudenzio, Nicolas 

Bérard, Marion 

Rogalla, Stephan 

Contag, Christopher H 

Bruhns, Pierre 

Galli, Stephen J 

U19 AI104209/AI/NIAID NIH HHS/United States 

R01 AI023990/AI/NIAID NIH HHS/United States 

R01 AR067145/AR/NIAMS NIH HHS/United States 

K99 AI110645/AI/NIAID NIH HHS/United States 

R01 CA072074/CA/NCI NIH HHS/United States 

UL1 RR025744/RR/NCRR NIH HHS/United States 

R37 AI023990/AI/NIAID NIH HHS/United States 

R21 NS080062/NS/NINDS NIH HHS/United States 

R01 AI070813/AI/NIAID NIH HHS/United States 

Research Support, N.I.H., Extramural 

Research Support, Non-U.S. Gov't 

J Exp Med. 2017 May 1;214(5):1249-1258. doi: 10.1084/jem.20161238. Epub 2017 Apr 6.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Imaging protective mast cells in living mice during severe contact hypersensitivity},

author = {Reber, L. L. and Sibilano, R. and Starkl, P. and Roers, A. and Grimbaldeston, M. A. and Tsai, M. and Gaudenzio, N. and Galli, S. J.},

year  = {2017},

date = {2017-01-01},

journal = {JCI Insight},

volume = {2},

number = {9},

abstract = {Contact hypersensitivity (CHS) is a common skin disease induced by epicutaneous sensitization to haptens. Conflicting results have been obtained regarding pathogenic versus protective roles of mast cells (MCs) in CHS, and this has been attributed in part to the limitations of certain models for studying MC functions in vivo. Here we describe a fluorescent imaging approach that enables in vivo selective labeling and tracking of MC secretory granules by real-time intravital 2-photon microscopy in living mice, and permits the identification of such MCs as a potential source of cytokines in different disease models. We show using this method that dermal MCs release their granules progressively into the surrounding microenvironment, but also represent an initial source of the antiinflammatory cytokine IL-10, during the early phase of severe CHS reactions. Finally, using 3 different types of MC-deficient mice, as well as mice in which IL-10 is ablated specifically in MCs, we show that IL-10 production by MCs can significantly limit the inflammation and tissue pathology observed in severe CHS reactions.},

note = {Reber, Laurent L 

Sibilano, Riccardo 

Starkl, Philipp 

Roers, Axel 

Grimbaldeston, Michele A 

Tsai, Mindy 

Gaudenzio, Nicolas 

Galli, Stephen J 

U19 AI104209/AI/NIAID NIH HHS/United States 

R01 AI023990/AI/NIAID NIH HHS/United States 

R01 AR067145/AR/NIAMS NIH HHS/United States 

K99 AI110645/AI/NIAID NIH HHS/United States 

R01 CA072074/CA/NCI NIH HHS/United States 

UL1 RR025744/RR/NCRR NIH HHS/United States 

R37 AI023990/AI/NIAID NIH HHS/United States 

R01 AI070813/AI/NIAID NIH HHS/United States 

JCI Insight. 2017 May 4;2(9):e92900. doi: 10.1172/jci.insight.92900. eCollection 2017 May 4.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Marichal2016,

title = {Guanine nucleotide exchange factor RABGEF1 regulates keratinocyte-intrinsic signaling to maintain skin homeostasis.},

author = {Marichal, Thomas and Gaudenzio, Nicolas and {El Abbas}, Sophie and Sibilano, Riccardo and Zurek, Oliwia and Starkl, Philipp and Reber, Laurent L and Pirottin, Dimitri and Kim, Jinah and Chambon, Pierre and Roers, Axel and Antoine, Nadine and Kawakami, Yuko and Kawakami, Toshiaki and Bureau, Fabrice and Tam, See-Ying and Tsai, Mindy and Galli, Stephen J},

doi = {10.1172/JCI86359},

issn = {1558-8238 (Electronic)},

year  = {2016},

date = {2016-12-01},

journal = {The Journal of clinical investigation},

volume = {126},

number = {12},

pages = {4497--4515},

abstract = {Epidermal keratinocytes form a structural and immune barrier that is essential for skin homeostasis. However, the mechanisms that regulate epidermal barrier function are incompletely understood. Here we have found that keratinocyte-specific deletion of the gene encoding RAB guanine nucleotide exchange factor 1 (RABGEF1, also known as RABEX-5) severely impairs epidermal barrier function in mice and induces an allergic cutaneous and systemic phenotype. RABGEF1-deficient keratinocytes exhibited aberrant activation of the intrinsic IL-1R/MYD88/NF-$kappa$B signaling pathway and MYD88-dependent abnormalities in expression of structural proteins that contribute to skin barrier function. Moreover, ablation of MYD88 signaling in RABGEF1-deficient keratinocytes or deletion of Il1r1 restored skin homeostasis and prevented development of skin inflammation. We further demonstrated that epidermal RABGEF1 expression is reduced in skin lesions of humans diagnosed with either atopic dermatitis or allergic contact dermatitis as well as in an inducible mouse model of allergic dermatitis. Our findings reveal a key role for RABGEF1 in dampening keratinocyte-intrinsic MYD88 signaling and sustaining epidermal barrier function in mice, and suggest that dysregulation of RABGEF1 expression may contribute to epidermal barrier dysfunction in allergic skin disorders in mice and humans. Thus, RABGEF1-mediated regulation of IL-1R/MYD88 signaling might represent a potential therapeutic target.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sibilano2016,

title = {A TNFRSF14-FcɛRI-mast cell pathway contributes to development of multiple features of asthma pathology in mice.},

author = {Sibilano, Riccardo and Gaudenzio, Nicolas and DeGorter, Marianne K and Reber, Laurent L and Hernandez, Joseph D and Starkl, Philipp M and Zurek, Oliwia W and Tsai, Mindy and Zahner, Sonja and Montgomery, Stephen B and Roers, Axel and Kronenberg, Mitchell and Yu, Mang and Galli, Stephen J},

doi = {10.1038/ncomms13696},

issn = {2041-1723 (Electronic)},

year  = {2016},

date = {2016-12-01},

journal = {Nature communications},

volume = {7},

pages = {13696},

abstract = {Asthma has multiple features, including airway hyperreactivity, inflammation and remodelling. The TNF superfamily member TNFSF14 (LIGHT), via interactions with the receptor TNFRSF14 (HVEM), can support T(H)2 cell generation and longevity and promote airway remodelling in mouse models of asthma, but the mechanisms by which TNFSF14 functions in this setting are incompletely understood. Here we find that mouse and human mast cells (MCs) express TNFRSF14 and that TNFSF14:TNFRSF14 interactions can enhance IgE-mediated MC signalling and mediator production. In mouse models of asthma, TNFRSF14 blockade with a neutralizing antibody administered after antigen sensitization, or genetic deletion of Tnfrsf14, diminishes plasma levels of antigen-specific IgG(1) and IgE antibodies, airway hyperreactivity, airway inflammation and airway remodelling. Finally, by analysing two types of genetically MC-deficient mice after engrafting MCs that either do or do not express TNFRSF14, we show that TNFRSF14 expression on MCs significantly contributes to the development of multiple features of asthma pathology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gaudenzio2016,

title = {Different activation signals induce distinct mast cell degranulation strategies.},

author = {Gaudenzio, Nicolas and Sibilano, Riccardo and Marichal, Thomas and Starkl, Philipp and Reber, Laurent L and Cenac, Nicolas and McNeil, Benjamin D and Dong, Xinzhong and Hernandez, Joseph D and Sagi-Eisenberg, Ronit and Hammel, Ilan and Roers, Axel and Valitutti, Salvatore and Tsai, Mindy and Espinosa, Eric and Galli, Stephen J},

doi = {10.1172/JCI85538},

issn = {1558-8238 (Electronic)},

year  = {2016},

date = {2016-10-01},

journal = {The Journal of clinical investigation},

volume = {126},

number = {10},

pages = {3981--3998},

abstract = {Mast cells (MCs) influence intercellular communication during inflammation by secreting cytoplasmic granules that contain diverse mediators. Here, we have demonstrated that MCs decode different activation stimuli into spatially and temporally distinct patterns of granule secretion. Certain signals, including substance P, the complement anaphylatoxins C3a and C5a, and endothelin 1, induced human MCs rapidly to secrete small and relatively spherical granule structures, a pattern consistent with the secretion of individual granules. Conversely, activating MCs with anti-IgE increased the time partition between signaling and secretion, which was associated with a period of sustained elevation of intracellular calcium and formation of larger and more heterogeneously shaped granule structures that underwent prolonged exteriorization. Pharmacological inhibition of IKK-$beta$ during IgE-dependent stimulation strongly reduced the time partition between signaling and secretion, inhibited SNAP23/STX4 complex formation, and switched the degranulation pattern into one that resembled degranulation induced by substance P. IgE-dependent and substance P-dependent activation in vivo also induced different patterns of mouse MC degranulation that were associated with distinct local and systemic pathophysiological responses. These findings show that cytoplasmic granule secretion from MCs that occurs in response to different activating stimuli can exhibit distinct dynamics and features that are associated with distinct patterns of MC-dependent inflammation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Khazen2016,

title = {Melanoma cell lysosome secretory burst neutralizes the CTL-mediated cytotoxicity at the lytic synapse.},

author = {Khazen, Roxana and M{ü}ller, Sabina and Gaudenzio, Nicolas and Espinosa, Eric and Puissegur, Marie-Pierre and Valitutti, Salvatore},

doi = {10.1038/ncomms10823},

issn = {2041-1723 (Electronic)},

year  = {2016},

date = {2016-03-01},

journal = {Nature communications},

volume = {7},

pages = {10823},

abstract = {Human melanoma cells express various tumour antigens that are recognized by CD8(+) cytotoxic T lymphocytes (CTLs) and elicit tumour-specific responses in vivo. However, natural and therapeutically enhanced CTL responses in melanoma patients are of limited efficacy. The mechanisms underlying CTL effector phase failure when facing melanomas are still largely elusive. Here we show that, on conjugation with CTL, human melanoma cells undergo an active late endosome/lysosome trafficking, which is intensified at the lytic synapse and is paralleled by cathepsin-mediated perforin degradation and deficient granzyme B penetration. Abortion of SNAP-23-dependent lysosomal trafficking, pH perturbation or impairment of lysosomal proteolytic activity restores susceptibility to CTL attack. Inside the arsenal of melanoma cell strategies to escape immune surveillance, we identify a self-defence mechanism based on exacerbated lysosome secretion and perforin degradation at the lytic synapse. Interfering with this synaptic self-defence mechanism might be useful in potentiating CTL-mediated therapies in melanoma patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Starkl2016,

title = {IgE antibodies, Fc$epsilon$RI$alpha$, and IgE-mediated local anaphylaxis can limit snake venom toxicity.},

author = {Starkl, Philipp and Marichal, Thomas and Gaudenzio, Nicolas and Reber, Laurent Lionel and Sibilano, Riccardo and Tsai, Mindy and Galli, Stephen Joseph},

doi = {10.1016/j.jaci.2015.08.005},

issn = {1097-6825 (Electronic)},

year  = {2016},

date = {2016-01-01},

journal = {The Journal of allergy and clinical immunology},

volume = {137},

number = {1},

pages = {246--257.e11},

abstract = {BACKGROUND: Type 2 cytokine-related immune responses associated with development of antigen-specific IgE antibodies can contribute to pathology in patients with allergic diseases and to fatal anaphylaxis. However, recent findings in mice indicate that IgE also can enhance defense against honeybee venom. OBJECTIVE: We tested whether IgE antibodies, IgE-dependent effector mechanisms, and a local anaphylactic reaction to an unrelated antigen can enhance defense against Russell viper venom (RVV) and determined whether such responses can be influenced by immunization protocol or mouse strain. METHODS: We compared the resistance of RVV-immunized wild-type, IgE-deficient, and Fcer1a-deficient mice after injection of a potentially lethal dose of RVV. RESULTS: A single prior exposure to RVV enhanced the ability of wild-type mice, but not mice lacking IgE or functional Fc$epsilon$RI, to survive challenge with a potentially lethal amount of RVV. Moreover, IgE-dependent local passive cutaneous anaphylaxis in response to challenge with an antigen not naturally present in RVV significantly enhanced resistance to the venom. Finally, we observed different effects on resistance to RVV or honeybee venom in BALB/c versus C57BL/6 mice that had received a second exposure to that venom before challenge with a high dose of that venom. CONCLUSION: These observations illustrate the potential benefit of IgE-dependent effector mechanisms in acquired host defense against venoms. The extent to which type 2 immune responses against venoms can decrease pathology associated with envenomation seems to be influenced by the type of venom, the frequency of venom exposure, and the genetic background of the host.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Different activation signals induce distinct mast cell degranulation strategies},

author = {Gaudenzio, N. and Sibilano, R. and Marichal, T. and Starkl, P. and Reber, L. L. and Cenac, N. and McNeil, B. D. and Dong, X. and Hernandez, J. D. and Sagi-Eisenberg, R. and Hammel, I. and Roers, A. and Valitutti, S. and Tsai, M. and Espinosa, E. and Galli, S. J.},

year  = {2016},

date = {2016-01-01},

journal = {J Clin Invest},

volume = {126},

number = {10},

pages = {3981-3998},

abstract = {Mast cells (MCs) influence intercellular communication during inflammation by secreting cytoplasmic granules that contain diverse mediators. Here, we have demonstrated that MCs decode different activation stimuli into spatially and temporally distinct patterns of granule secretion. Certain signals, including substance P, the complement anaphylatoxins C3a and C5a, and endothelin 1, induced human MCs rapidly to secrete small and relatively spherical granule structures, a pattern consistent with the secretion of individual granules. Conversely, activating MCs with anti-IgE increased the time partition between signaling and secretion, which was associated with a period of sustained elevation of intracellular calcium and formation of larger and more heterogeneously shaped granule structures that underwent prolonged exteriorization. Pharmacological inhibition of IKK-β during IgE-dependent stimulation strongly reduced the time partition between signaling and secretion, inhibited SNAP23/STX4 complex formation, and switched the degranulation pattern into one that resembled degranulation induced by substance P. IgE-dependent and substance P-dependent activation in vivo also induced different patterns of mouse MC degranulation that were associated with distinct local and systemic pathophysiological responses. These findings show that cytoplasmic granule secretion from MCs that occurs in response to different activating stimuli can exhibit distinct dynamics and features that are associated with distinct patterns of MC-dependent inflammation.},

note = {Gaudenzio, Nicolas 

Sibilano, Riccardo 

Marichal, Thomas 

Starkl, Philipp 

Reber, Laurent L 

Cenac, Nicolas 

McNeil, Benjamin D 

Dong, Xinzhong 

Hernandez, Joseph D 

Sagi-Eisenberg, Ronit 

Hammel, Ilan 

Roers, Axel 

Valitutti, Salvatore 

Tsai, Mindy 

Espinosa, Eric 

Galli, Stephen J 

U19 AI104209/AI/NIAID NIH HHS/United States 

P30 NS069375/NS/NINDS NIH HHS/United States 

R01 AI023990/AI/NIAID NIH HHS/United States 

R01 CA072074/CA/NCI NIH HHS/United States 

UL1 RR025744/RR/NCRR NIH HHS/United States 

R37 AI023990/AI/NIAID NIH HHS/United States 

R01 AI070813/AI/NIAID NIH HHS/United States 

S10 RR026780/RR/NCRR NIH HHS/United States 

J Clin Invest. 2016 Oct 3;126(10):3981-3998. doi: 10.1172/JCI85538. Epub 2016 Sep 19.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Melanoma cell lysosome secretory burst neutralizes the CTL-mediated cytotoxicity at the lytic synapse},

author = {Khazen, R. and Müller, S. and Gaudenzio, N. and Espinosa, E. and Puissegur, M. P. and Valitutti, S.},

year  = {2016},

date = {2016-01-01},

journal = {Nat Commun},

volume = {7},

pages = {10823},

abstract = {Human melanoma cells express various tumour antigens that are recognized by CD8(+) cytotoxic T lymphocytes (CTLs) and elicit tumour-specific responses in vivo. However, natural and therapeutically enhanced CTL responses in melanoma patients are of limited efficacy. The mechanisms underlying CTL effector phase failure when facing melanomas are still largely elusive. Here we show that, on conjugation with CTL, human melanoma cells undergo an active late endosome/lysosome trafficking, which is intensified at the lytic synapse and is paralleled by cathepsin-mediated perforin degradation and deficient granzyme B penetration. Abortion of SNAP-23-dependent lysosomal trafficking, pH perturbation or impairment of lysosomal proteolytic activity restores susceptibility to CTL attack. Inside the arsenal of melanoma cell strategies to escape immune surveillance, we identify a self-defence mechanism based on exacerbated lysosome secretion and perforin degradation at the lytic synapse. Interfering with this synaptic self-defence mechanism might be useful in potentiating CTL-mediated therapies in melanoma patients.},

note = {Khazen, Roxana 

Müller, Sabina 

Gaudenzio, Nicolas 

Espinosa, Eric 

Puissegur, Marie-Pierre 

Valitutti, Salvatore 

Research Support, Non-U.S. Gov't 

Nat Commun. 2016 Mar 4;7:10823. doi: 10.1038/ncomms10823.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Guanine nucleotide exchange factor RABGEF1 regulates keratinocyte-intrinsic signaling to maintain skin homeostasis},

author = {Marichal, T. and Gaudenzio, N. and El Abbas, S. and Sibilano, R. and Zurek, O. and Starkl, P. and Reber, L. L. and Pirottin, D. and Kim, J. and Chambon, P. and Roers, A. and Antoine, N. and Kawakami, Y. and Kawakami, T. and Bureau, F. and Tam, S. Y. and Tsai, M. and Galli, S. J.},

year  = {2016},

date = {2016-01-01},

journal = {J Clin Invest},

volume = {126},

number = {12},

pages = {4497-4515},

abstract = {Epidermal keratinocytes form a structural and immune barrier that is essential for skin homeostasis. However, the mechanisms that regulate epidermal barrier function are incompletely understood. Here we have found that keratinocyte-specific deletion of the gene encoding RAB guanine nucleotide exchange factor 1 (RABGEF1, also known as RABEX-5) severely impairs epidermal barrier function in mice and induces an allergic cutaneous and systemic phenotype. RABGEF1-deficient keratinocytes exhibited aberrant activation of the intrinsic IL-1R/MYD88/NF-κB signaling pathway and MYD88-dependent abnormalities in expression of structural proteins that contribute to skin barrier function. Moreover, ablation of MYD88 signaling in RABGEF1-deficient keratinocytes or deletion of Il1r1 restored skin homeostasis and prevented development of skin inflammation. We further demonstrated that epidermal RABGEF1 expression is reduced in skin lesions of humans diagnosed with either atopic dermatitis or allergic contact dermatitis as well as in an inducible mouse model of allergic dermatitis. Our findings reveal a key role for RABGEF1 in dampening keratinocyte-intrinsic MYD88 signaling and sustaining epidermal barrier function in mice, and suggest that dysregulation of RABGEF1 expression may contribute to epidermal barrier dysfunction in allergic skin disorders in mice and humans. Thus, RABGEF1-mediated regulation of IL-1R/MYD88 signaling might represent a potential therapeutic target.},

note = {Marichal, Thomas 

Gaudenzio, Nicolas 

El Abbas, Sophie 

Sibilano, Riccardo 

Zurek, Oliwia 

Starkl, Philipp 

Reber, Laurent L 

Pirottin, Dimitri 

Kim, Jinah 

Chambon, Pierre 

Roers, Axel 

Antoine, Nadine 

Kawakami, Yuko 

Kawakami, Toshiaki 

Bureau, Fabrice 

Tam, See-Ying 

Tsai, Mindy 

Galli, Stephen J 

T32 AI007290/AI/NIAID NIH HHS/United States 

R01 HL124283/HL/NHLBI NIH HHS/United States 

R01 AI023990/AI/NIAID NIH HHS/United States 

R01 AR067145/AR/NIAMS NIH HHS/United States 

K99 AI110645/AI/NIAID NIH HHS/United States 

R01 CA072074/CA/NCI NIH HHS/United States 

R37 AI023990/AI/NIAID NIH HHS/United States 

R01 AI070813/AI/NIAID NIH HHS/United States 

R01 AR064418/AR/NIAMS NIH HHS/United States 

Research Support, N.I.H., Extramural 

Research Support, Non-U.S. Gov't 

J Clin Invest. 2016 Dec 1;126(12):4497-4515. doi: 10.1172/JCI86359. Epub 2016 Nov 7.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {Neutrophils are not required for resolution of acute gouty arthritis in mice},

author = {Reber, L. L. and Gaudenzio, N. and Starkl, P. and Galli, S. J.},

year  = {2016},

date = {2016-01-01},

journal = {Nat Med},

volume = {22},

number = {12},

pages = {1382-1384},

note = {Reber, Laurent L 

Gaudenzio, Nicolas 

Starkl, Philipp 

Galli, Stephen J 

K99 AI110645/AI/NIAID NIH HHS/United States 

R01 AR067145/AR/NIAMS NIH HHS/United States 

U19 AI104209/AI/NIAID NIH HHS/United States 

R21 NS080062/NS/NINDS NIH HHS/United States 

Comment 

Letter 

Research Support, N.I.H., Extramural 

Research Support, Non-U.S. Gov't 

United States 

Nat Med. 2016 Dec 6;22(12):1382-1384. doi: 10.1038/nm.4216.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {A TNFRSF14-FcɛRI-mast cell pathway contributes to development of multiple features of asthma pathology in mice},

author = {Sibilano, R. and Gaudenzio, N. and DeGorter, M. K. and Reber, L. L. and Hernandez, J. D. and Starkl, P. M. and Zurek, O. W. and Tsai, M. and Zahner, S. and Montgomery, S. B. and Roers, A. and Kronenberg, M. and Yu, M. and Galli, S. J.},

year  = {2016},

date = {2016-01-01},

journal = {Nat Commun},

volume = {7},

pages = {13696},

abstract = {Asthma has multiple features, including airway hyperreactivity, inflammation and remodelling. The TNF superfamily member TNFSF14 (LIGHT), via interactions with the receptor TNFRSF14 (HVEM), can support T(H)2 cell generation and longevity and promote airway remodelling in mouse models of asthma, but the mechanisms by which TNFSF14 functions in this setting are incompletely understood. Here we find that mouse and human mast cells (MCs) express TNFRSF14 and that TNFSF14:TNFRSF14 interactions can enhance IgE-mediated MC signalling and mediator production. In mouse models of asthma, TNFRSF14 blockade with a neutralizing antibody administered after antigen sensitization, or genetic deletion of Tnfrsf14, diminishes plasma levels of antigen-specific IgG(1) and IgE antibodies, airway hyperreactivity, airway inflammation and airway remodelling. Finally, by analysing two types of genetically MC-deficient mice after engrafting MCs that either do or do not express TNFRSF14, we show that TNFRSF14 expression on MCs significantly contributes to the development of multiple features of asthma pathology.},

note = {Sibilano, Riccardo 

Gaudenzio, Nicolas 

DeGorter, Marianne K 

Reber, Laurent L 

Hernandez, Joseph D 

Starkl, Philipp M 

Zurek, Oliwia W 

Tsai, Mindy 

Zahner, Sonja 

Montgomery, Stephen B 

Roers, Axel 

Kronenberg, Mitchell 

Yu, Mang 

Galli, Stephen J 

T32 AI007290/AI/NIAID NIH HHS/United States 

Research Support, N.I.H., Extramural 

Research Support, Non-U.S. Gov't 

Nat Commun. 2016 Dec 16;7:13696. doi: 10.1038/ncomms13696.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {IgE antibodies, FcεRIα, and IgE-mediated local anaphylaxis can limit snake venom toxicity},

author = {Starkl, P. and Marichal, T. and Gaudenzio, N. and Reber, L. L. and Sibilano, R. and Tsai, M. and Galli, S. J.},

year  = {2016},

date = {2016-01-01},

journal = {J Allergy Clin Immunol},

volume = {137},

number = {1},

pages = {246-257 e11},

abstract = {BACKGROUND: Type 2 cytokine-related immune responses associated with development of antigen-specific IgE antibodies can contribute to pathology in patients with allergic diseases and to fatal anaphylaxis. However, recent findings in mice indicate that IgE also can enhance defense against honeybee venom. OBJECTIVE: We tested whether IgE antibodies, IgE-dependent effector mechanisms, and a local anaphylactic reaction to an unrelated antigen can enhance defense against Russell viper venom (RVV) and determined whether such responses can be influenced by immunization protocol or mouse strain. METHODS: We compared the resistance of RVV-immunized wild-type, IgE-deficient, and Fcer1a-deficient mice after injection of a potentially lethal dose of RVV. RESULTS: A single prior exposure to RVV enhanced the ability of wild-type mice, but not mice lacking IgE or functional FcεRI, to survive challenge with a potentially lethal amount of RVV. Moreover, IgE-dependent local passive cutaneous anaphylaxis in response to challenge with an antigen not naturally present in RVV significantly enhanced resistance to the venom. Finally, we observed different effects on resistance to RVV or honeybee venom in BALB/c versus C57BL/6 mice that had received a second exposure to that venom before challenge with a high dose of that venom. CONCLUSION: These observations illustrate the potential benefit of IgE-dependent effector mechanisms in acquired host defense against venoms. The extent to which type 2 immune responses against venoms can decrease pathology associated with envenomation seems to be influenced by the type of venom, the frequency of venom exposure, and the genetic background of the host.},

note = {Starkl, Philipp 

Marichal, Thomas 

Gaudenzio, Nicolas 

Reber, Laurent Lionel 

Sibilano, Riccardo 

Tsai, Mindy 

Galli, Stephen Joseph 

R01 AI023990/AI/NIAID NIH HHS/United States 

CA072074/CA/NCI NIH HHS/United States 

K99 AI110645/AI/NIAID NIH HHS/United States 

AI070813/AI/NIAID NIH HHS/United States 

AI023990/AI/NIAID NIH HHS/United States 

R01 CA072074/CA/NCI NIH HHS/United States 

K99AI110645/AI/NIAID NIH HHS/United States 

UL1 RR025744/RR/NCRR NIH HHS/United States 

UL1 TR001085/TR/NCATS NIH HHS/United States 

R37 AI023990/AI/NIAID NIH HHS/United States 

R01 AI070813/AI/NIAID NIH HHS/United States 

Research Support, N.I.H., Extramural 

Research Support, Non-U.S. Gov't 

J Allergy Clin Immunol. 2016 Jan;137(1):246-257.e11. doi: 10.1016/j.jaci.2015.08.005. Epub 2015 Sep 26.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{d,

title = {(No Title)},

url = {http://science.sciencemag.org/},

doi = {10.1126/science.abf2022},

keywords = {},

pubstate = {published},

tppubtype = {article}

}