Neural regulation of immune response

   Coordinator : N. GAUDENZIO

Scientific objectives

 


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. On top of their function of signal transmission to the spinal cord and brain, peripheral neurons (including afferent neurons) can also directly sense environmental alarms and consequently regulate the development of various type of immune responses. At the IMMCEPTION LAB, Nicolas GAUDENZIO and his team combine unique genetic models and new intravital imaging approaches to study how neuro-immune interactions can regulate the development of inflammatory reactions in various pathological contexts. 

Our Projects


AXE 1: Neuro-immuno interactions in health and disease

Communication between brain and immune system plays a critical role in both physiology and pathology. Neuro-immunology is a new emerging field in biomedical research, as crosstalk between the brain and immune system orchestrates different important types of responses, e.g. the response to bacterial infections within several major barrier tissues, including the skin, lung and the intestinal tract. In the skin, cutaneous nerves play an integral role in modulating bacterial host defences. Cutaneous sensory neurons can sense a wide variety of stimuli, such as heat, chemicals, mechanical stimulation, inflammatory cytokines, and microbial products. Despite their primary function of transmission of sensations, sensory neurons (in particular nociceptors) have been shown to be also potent regulators of immune responses.

A major focus of our lab is to identify molecular mechanisms regulating neuro-immune interactions during allergic skin inflammation (such as atopic dermatitis) and to develop new intravital and multiplex imaging methods to probe such interactions in preclinical models.

AXE 2: Skin aging

The project focuses on the biology of skin aging and is part of the INSPIRE Bio-resource Research Platform for Healthy Aging (INSPIRE platform research initiative, RC31/19/0236) which aims to investigate the interplays between biological aging and the severity of burdensome chronic conditions during aging. The skin is the organ where signs of aging are visible, and thus and indicator of an individual’s health. The main objective of the project is to identify key biomarkers in the skin that are representative of healthy or pathological aging by combining different next generation omics in a cohort of patients from different ages.

AXE 3: Rheumatoid autoimmunity: Autoantibodies against citrullinated proteins - physiopathology

Anti-citrullinated protein autoantibodies (ACPA) : pathophysiology of Rheumatoid Arthritis

The goal of our group is to understand the role played by the autoimmune response to citrullinated proteins in the pathophysiology of rheumatoid arthritis (RA).

Such response translates into the production of anti-citrullinated protein autoantibodies (ACPA), which are notably synthesized in RA joints by plasmocytes of the synovial membrane where an autoantigenic target, citrullinated fibrin, is also abundant.

Presently, our studies are devoted to understanding the contribution to RA synovitis of the disease-specific immune complexes (IC) that form in the synovial membrane following the interaction of ACPA with citrullinated fibrin (ACPA IC). In this tissue, macrophages considerably contribute to inflammation and joint destruction notably because they constitute a major source of tumor necrosis factor (TNF)-α which is a key pro-inflammatory cytokine in the disease. We therefore developed a totally human in vitro model in which monocyte-derived macrophages are stimulated by IC formed between patient-derived ACPA and immobilized citrullinated human fibrinogen.

This model contributed to supporting the hypothesis of the pathophysiological involvement of ACPA as it established the inflammatory potential of ACPA IC by showing they induce TNF-α secretion in which the activating FcgγRII IgG receptor has a major contribution.

Our current projects include the study of the influence of another RA-associated autoantibody, rheumatoid factor, and of the macrophage phenotype on the response to ACPA IC.

ban

Photograph and radiograph of the hands and wrists of a patient with rheumatoid arthritis (left and centre)
Schematic representation of the interaction between ACPA IC and synovial macrophages (right)

 


Anti-citrullinated protein auto-antibodies : diagnosis and specific immunotherapy

Our group is involved in the study of the rheumatoid arthritis (RA)-specific autoantibodies directed to citrullinated proteins (ACPAs). ACPAs have a high diagnostic value. They are present in up to 80% of sera from RA-patients with a specificity > 98%.

Our laboratory has largely contributed to the characterization of the antigenic targets of ACPAs. In 2001, we identified citrullinated forms of the α- and β-chains of fibrin as major targets of ACPA in the synovial tissue of RA patients. However, several other citrullinated proteins have been shown to be reactive with ACPA in vitro and some of them have been proposed as possible in vivo targets. Our current work aims to demonstrate that there is only one family of ACPA, that their major antigenic target corresponds to citrullinated forms of fibrin and that these autoantibodies variously crossreact with other citrullinated proteins depending on the considered patient serum.

More recently, we identified two peptides α36-50 and β60-74 as bearing the immunodominant epitopes of citrullinated fibrin. Then, we defined three 4- and 5-amino acid-long minimal epitopes that together almost entirely encompass the reactivity of ACPA to citrullinated fibrin for a vast majority of RA-sera. We underwent to develop tests for the detection of each subfamily of ACPA directed to each of those 3 minimal epitopes. These tests will allow to define different groups of patients according to the reactivity of their sera to the 3 minimal epitopes and to evaluate the prognostic value and the predictive value for the response to treatment of ACPA directed to each immunodominant epitope. We are also studying the evolution of the ACPA titer and specificity in response to treatment by anti-CD20 antibodies.

Position of immunoreactive peptides on a schematic ribbon representation of the 3D structure of the fibrinogen molecule

(Eur J Immunol 2006, 36:2250).

 

 

Other information


 

Publications

2021

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

Title: IgE antibodies increase honeybee venom responsiveness and detoxification efficiency of mast cells Authors Journal Article

2021.

Abstract | Links | BibTeX

Serhan, Nadine ; Cenac, Nicolas ; Basso, Lilian ; Gaudenzio, Nicolas

Mas-related G protein-coupled receptors (Mrgprs) - Key regulators of neuroimmune interactions Journal Article

Neuroscience Letters, 2021, ISSN: 03043940.

Links | BibTeX

Tauber, Marie ; Wang, Fang ; Kim, Brian ; Gaudenzio, Nicolas ; Blank, Ulrich ; Kawakami, Toshiaki

Bidirectional sensory neuron-immune interactions: a new vision in the understanding of allergic inflammation Journal Article

Current Opinion in Immunology, 72 , pp. 79–86, 2021.

Abstract | Links | BibTeX

Corbière, A; Loste, A; Gaudenzio, N

MRGPRX2 sensing of cationic compounds-A bridge between nociception and skin diseases? Journal Article

Exp Dermatol, 30 (2), pp. 193-200, 2021, (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.).

Abstract | BibTeX

Serhan, N; Cenac, N; Basso, L; Gaudenzio, N

Mas-related G protein-coupled receptors (Mrgprs) - Key regulators of neuroimmune interactions Journal Article

Neurosci Lett, 749 , pp. 135724, 2021, (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.).

Abstract | BibTeX

Starkl, P; Gaudenzio, N; Marichal, T; Reber, L L; Sibilano, R; Watzenboeck, M L; Fontaine, F; Mueller, A C; Tsai, M; Knapp, S; Galli, S J

IgE antibodies increase honeybee venom responsiveness and detoxification efficiency of mast cells Journal Article

Allergy, 2021, (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.).

Abstract | BibTeX

Tauber, M; Wang, F; Kim, B; Gaudenzio, N

Bidirectional sensory neuron-immune interactions: a new vision in the understanding of allergic inflammation Journal Article

Curr Opin Immunol, 72 , pp. 79-86, 2021, (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.).

Abstract | BibTeX

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

Dual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice Journal Article

Nature Communications, 12 , pp. 2574, 2021, ISSN: 2041-1723.

Abstract | Links | BibTeX

2020

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, Fr{é}d{é}ric ; Mueller, Andr{é} C; Amieva, Manuel R; Galli, Stephen J; Knapp, Sylvia

IgE Effector Mechanisms, in Concert with Mast Cells, Contribute to Acquired Host Defense against Staphylococcusaureus. Journal Article

Immunity, 53 (4), pp. 793–804.e9, 2020, ISSN: 1097-4180 (Electronic).

Abstract | Links | BibTeX

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

Omalizumab in the treatment of adult patients with mastocytosis: A systematic review. Journal Article

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 50 (6), pp. 654–661, 2020, ISSN: 1365-2222 (Electronic).

Abstract | Links | BibTeX

Folkerts, Jelle ; Gaudenzio, Nicolas ; Maurer, Marcus ; Hendriks, Rudi W; Stadhouders, Ralph ; Tam, See-Ying ; Galli, Stephen J

Rapid identification of human mast cell degranulation regulators using functional genomics coupled to high-resolution confocal microscopy. Journal Article

Nature protocols, 15 (3), pp. 1285–1310, 2020, ISSN: 1750-2799 (Electronic).

Abstract | Links | BibTeX

Meixiong, James ; Basso, Lilian ; Dong, Xinzhong ; Gaudenzio, Nicolas

Nociceptor-Mast Cell Sensory Clusters as Regulators of Skin Homeostasis. Journal Article

Trends in neurosciences, 43 (3), pp. 130–132, 2020, ISSN: 1878-108X (Electronic).

Abstract | Links | BibTeX

Corbi{è}re, Auriane ; Loste, Alexia ; Gaudenzio, Nicolas

MRGPRX2 sensing of cationic compounds—A bridge between nociception and skin diseases? Journal Article

Experimental Dermatology, 2020, ISSN: 16000625.

Abstract | Links | BibTeX

Galli, Stephen J; Gaudenzio, Nicolas; Tsai, Mindy

Mast Cells in Inflammation and Disease: Recent Progress and Ongoing Concerns Journal Article

Annual Review of Immunology, 5 , 2020.

Abstract | Links | BibTeX

Arock, M; Blank, U; Charles, N; Gaudenzio, N; Georgin-Lavialle, S; Li, M; Ménasché, G; Reber, L; Vitte, J

The "Mast Cell and Basophil Club" of the French Society for Immunology Journal Article

Eur J Immunol, 50 (10), pp. 1430-1431, 2020, (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.).

BibTeX

Folkerts, J; Gaudenzio, N; Maurer, M; Hendriks, R W; Stadhouders, R; Tam, S Y; Galli, S J

Rapid identification of human mast cell degranulation regulators using functional genomics coupled to high-resolution confocal microscopy Journal Article

Nat Protoc, 15 (3), pp. 1285-1310, 2020, (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.).

Abstract | BibTeX

Galli, S J; Gaudenzio, N; Tsai, M

Mast Cells in Inflammation and Disease: Recent Progress and Ongoing Concerns Journal Article

Annu Rev Immunol, 38 , pp. 49-77, 2020, (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.).

Abstract | BibTeX

Jendoubi, F; Gaudenzio, N; Gallini, A; Negretto, M; Paul, C; Bulai Livideanu, C

Omalizumab in the treatment of adult patients with mastocytosis: A systematic review Journal Article

Clin Exp Allergy, 50 (6), pp. 654-661, 2020, (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.).

Abstract | BibTeX

Meixiong, J; Basso, L; Dong, X; Gaudenzio, N

Nociceptor-Mast Cell Sensory Clusters as Regulators of Skin Homeostasis Journal Article

Trends Neurosci, 43 (3), pp. 130-132, 2020, (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.).

Abstract | BibTeX

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

IgE Effector Mechanisms, in Concert with Mast Cells, Contribute to Acquired Host Defense against Staphylococcusaureus Journal Article

Immunity, 53 (4), pp. 793-804 e9, 2020, (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.).

Abstract | BibTeX

2019

Basso, Lilian ; Serhan, Nadine ; Tauber, Marie ; Gaudenzio, Nicolas

Peripheral neurons: Master regulators of skin and mucosal immune response. Journal Article

European journal of immunology, 49 (11), pp. 1984–1997, 2019, ISSN: 1521-4141 (Electronic).

Abstract | Links | BibTeX

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

A Connective Tissue Mast-Cell-Specific Receptor Detects Bacterial Quorum-Sensing Molecules and Mediates Antibacterial Immunity. Journal Article

Cell host & microbe, 26 (1), pp. 114–122.e8, 2019, ISSN: 1934-6069 (Electronic).

Abstract | Links | BibTeX

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

House dust mites activate nociceptor–mast cell clusters to drive type 2 skin inflammation Journal Article

Nature Immunology, 2019, ISSN: 15292916.

Abstract | Links | BibTeX

Basso, L; Serhan, N; Tauber, M; Gaudenzio, N

Peripheral neurons: Master regulators of skin and mucosal immune response Journal Article

Eur J Immunol, 49 (11), pp. 1984-1997, 2019, (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.).

Abstract | BibTeX

Serhan, N; Basso, L; Sibilano, R; Petitfils, C; Meixiong, J; Bonnart, C; Reber, L L; Marichal, T; Starkl, P; Cenac, N; Dong, X; Tsai, M; Galli, S J; Gaudenzio, N

House dust mites activate nociceptor-mast cell clusters to drive type 2 skin inflammation Journal Article

Nat Immunol, 20 (11), pp. 1435-1443, 2019, (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.).

Abstract | BibTeX

2018

Gaudenzio, Nicolas ; Marichal, Thomas ; Galli, Stephen J; Reber, Laurent L

Genetic and Imaging Approaches Reveal Pro-Inflammatory and Immunoregulatory Roles of Mast Cells in Contact Hypersensitivity. Journal Article

Frontiers in immunology, 9 , pp. 1275, 2018, ISSN: 1664-3224 (Print).

Abstract | Links | BibTeX

Galli, Stephen J; Gaudenzio, Nicolas

Human mast cells as antigen-presenting cells: When is this role important in vivo? Miscellaneous

2018, ISSN: 1097-6825 (Electronic).

Links | BibTeX

Galli, S J; Gaudenzio, N

Human mast cells as antigen-presenting cells: When is this role important in vivo? Journal Article

J Allergy Clin Immunol, 141 (1), pp. 92-93, 2018, (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.).

BibTeX

Gaudenzio, N; Marichal, T; Galli, S J; Reber, L L

Genetic and Imaging Approaches Reveal Pro-Inflammatory and Immunoregulatory Roles of Mast Cells in Contact Hypersensitivity Journal Article

Front Immunol, 9 , pp. 1275, 2018, (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.).

Abstract | BibTeX

2017

Reber, Laurent L; Sibilano, Riccardo ; Starkl, Philipp ; Roers, Axel ; Grimbaldeston, Michele A; Tsai, Mindy ; Gaudenzio, Nicolas ; Galli, Stephen J

Imaging protective mast cells in living mice during severe contact hypersensitivity. Journal Article

JCI insight, 2 (9), 2017, ISSN: 2379-3708 (Electronic).

Abstract | Links | BibTeX

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

Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide. Journal Article

The Journal of experimental medicine, 214 (5), pp. 1249–1258, 2017, ISSN: 1540-9538 (Electronic).

Abstract | Links | BibTeX

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, Christopher K

Decoupling the Functional Pleiotropy of Stem Cell Factor by Tuning c-Kit Signaling. Journal Article

Cell, 168 (6), pp. 1041–1052.e18, 2017, ISSN: 1097-4172 (Electronic).

Abstract | Links | BibTeX

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

Assessing basophil activation by using flow cytometry and mass cytometry in blood stored 24 hours before analysis. Journal Article

The Journal of allergy and clinical immunology, 139 (3), pp. 889–899.e11, 2017, ISSN: 1097-6825 (Electronic).

Abstract | Links | BibTeX

Balbino, Bianca ; Sibilano, Riccardo ; Starkl, Philipp ; Marichal, Thomas ; Gaudenzio, Nicolas ; Karasuyama, Hajime ; Bruhns, Pierre ; Tsai, Mindy ; Reber, Laurent L; Galli, Stephen J

Pathways of immediate hypothermia and leukocyte infiltration in an adjuvant-free mouse model of anaphylaxis. Journal Article

The Journal of allergy and clinical immunology, 139 (2), pp. 584–596.e10, 2017, ISSN: 1097-6825 (Electronic).

Abstract | Links | BibTeX

Balbino, B; Sibilano, R; Starkl, P; Marichal, T; Gaudenzio, N; Karasuyama, H; Bruhns, P; Tsai, M; Reber, L L; Galli, S J

Pathways of immediate hypothermia and leukocyte infiltration in an adjuvant-free mouse model of anaphylaxis Journal Article

J Allergy Clin Immunol, 139 (2), pp. 584-596 e10, 2017, (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.).

Abstract | BibTeX

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

Decoupling the Functional Pleiotropy of Stem Cell Factor by Tuning c-Kit Signaling Journal Article

Cell, 168 (6), pp. 1041-1052 e18, 2017, (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.).

Abstract | BibTeX

Mukai, K; Gaudenzio, N; Gupta, S; Vivanco, N; Bendall, S C; Maecker, H T; Chinthrajah, R S; Tsai, M; Nadeau, K C; Galli, S J

Assessing basophil activation by using flow cytometry and mass cytometry in blood stored 24 hours before analysis Journal Article

J Allergy Clin Immunol, 139 (3), pp. 889-899 e11, 2017, (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.).

Abstract | BibTeX

Reber, L L; Gillis, C M; Starkl, P; Jönsson, F; Sibilano, R; Marichal, T; Gaudenzio, N; Bérard, M; Rogalla, S; Contag, C H; Bruhns, P; Galli, S J

Neutrophil myeloperoxidase diminishes the toxic effects and mortality induced by lipopolysaccharide Journal Article

J Exp Med, 214 (5), pp. 1249-1258, 2017, (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.).

Abstract | BibTeX

Reber, L L; Sibilano, R; Starkl, P; Roers, A; Grimbaldeston, M A; Tsai, M; Gaudenzio, N; Galli, S J

Imaging protective mast cells in living mice during severe contact hypersensitivity Journal Article

JCI Insight, 2 (9), 2017, (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.).

Abstract | BibTeX

2016

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

Guanine nucleotide exchange factor RABGEF1 regulates keratinocyte-intrinsic signaling to maintain skin homeostasis. Journal Article

The Journal of clinical investigation, 126 (12), pp. 4497–4515, 2016, ISSN: 1558-8238 (Electronic).

Abstract | Links | BibTeX

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

A TNFRSF14-FcɛRI-mast cell pathway contributes to development of multiple features of asthma pathology in mice. Journal Article

Nature communications, 7 , pp. 13696, 2016, ISSN: 2041-1723 (Electronic).

Abstract | Links | BibTeX

Reber, Laurent L; Gaudenzio, Nicolas ; Starkl, Philipp ; Galli, Stephen J

Neutrophils are not required for resolution of acute gouty arthritis in mice. Miscellaneous

2016, ISSN: 1546-170X (Electronic).

Links | BibTeX

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

Different activation signals induce distinct mast cell degranulation strategies. Journal Article

The Journal of clinical investigation, 126 (10), pp. 3981–3998, 2016, ISSN: 1558-8238 (Electronic).

Abstract | Links | BibTeX

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

Melanoma cell lysosome secretory burst neutralizes the CTL-mediated cytotoxicity at the lytic synapse. Journal Article

Nature communications, 7 , pp. 10823, 2016, ISSN: 2041-1723 (Electronic).

Abstract | Links | BibTeX

Starkl, Philipp ; Marichal, Thomas ; Gaudenzio, Nicolas ; Reber, Laurent Lionel ; Sibilano, Riccardo ; Tsai, Mindy ; Galli, Stephen Joseph

IgE antibodies, Fc$epsilon$RI$alpha$, and IgE-mediated local anaphylaxis can limit snake venom toxicity. Journal Article

The Journal of allergy and clinical immunology, 137 (1), pp. 246–257.e11, 2016, ISSN: 1097-6825 (Electronic).

Abstract | Links | BibTeX

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

Different activation signals induce distinct mast cell degranulation strategies Journal Article

J Clin Invest, 126 (10), pp. 3981-3998, 2016, (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.).

Abstract | BibTeX

Khazen, R; Müller, S; Gaudenzio, N; Espinosa, E; Puissegur, M P; Valitutti, S

Melanoma cell lysosome secretory burst neutralizes the CTL-mediated cytotoxicity at the lytic synapse Journal Article

Nat Commun, 7 , pp. 10823, 2016, (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.).

Abstract | BibTeX

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

Guanine nucleotide exchange factor RABGEF1 regulates keratinocyte-intrinsic signaling to maintain skin homeostasis Journal Article

J Clin Invest, 126 (12), pp. 4497-4515, 2016, (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.).

Abstract | BibTeX

Reber, L L; Gaudenzio, N; Starkl, P; Galli, S J

Neutrophils are not required for resolution of acute gouty arthritis in mice Journal Article

Nat Med, 22 (12), pp. 1382-1384, 2016, (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.).

BibTeX

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

A TNFRSF14-FcɛRI-mast cell pathway contributes to development of multiple features of asthma pathology in mice Journal Article

Nat Commun, 7 , pp. 13696, 2016, (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.).

Abstract | BibTeX

Starkl, P; Marichal, T; Gaudenzio, N; Reber, L L; Sibilano, R; Tsai, M; Galli, S J

IgE antibodies, FcεRIα, and IgE-mediated local anaphylaxis can limit snake venom toxicity Journal Article

J Allergy Clin Immunol, 137 (1), pp. 246-257 e11, 2016, (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.).

Abstract | BibTeX

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Links | BibTeX

Impact on society

Atopic dermatitis is an inflammatory skin disease that affects up to 20% of children and 5% of adults in Western countries. The quality of life of these people is affected by pain and severe itching. Our research activity aims to create a synergy between several disciplines to better understand the causes of the disease and to assess how immune cells interact with other components, in particular with nerve fibers.

Collaborations

External
Xinzhong Dong, Johns Hopkins University, USA
Stephen J Galli & Mindy Tsai, Stanford University, USA
Christophe Altier, University of Calgary, Canada
Rebecca Gentek, University of Edinburg, Scotland
Thomas Marichal, University of Liege, Belgium
Gunnar Pejler, Uppsala University, Sweden
Vassilis Pachnis, The Francis Crick Institute, King’s College, London, UK
Philipp Starkl, University of Vienna, Austria
Nicolas Cenac & Gilles Dietrich, IRSD Inserm, Toulouse, France
Claude Knauf, IRSD Inserm, Toulouse, France
Jean François Nicolas & Audrey Nosbaum, Lyon University Hospital, France
Genoskin Inc, Toulouse, France
Pierre Fabre, Toulouse, France

Internal
Laurent Reber, Infinity, Toulouse, France
Michel Simon, Infinity, Toulouse, France
Nicolas Fazilleau, Infinity, Toulouse, France
Nicolas Blanchard, Infinity, Toulouse, France
Carle Paul, Toulouse University Hospital & Infinity, France

News feed

We are thrilled to announce that our PhD student, Nadine Serhan from Lebanon, just received the L’Oreal-Unesco Award for Women in Science for her brilliant PhD. Congrats Nadine!
http://www.occitanie-pyrenees.inserm.fr/actualites/nadine-serhan-laureate-du-prix-l-oreal

 

 

Thanks a lot to the media « La Dépêche » for this nice article about atopic eczema destined to an audience of non specialist.
https://www.ladepeche.fr/2020/09/15/comprendre-leczema-atopique-cette-maladie-qui-gache-la-vie-de-milliers-de-personnes-9072614.php

 

 

Our last invited review on the role of mast cells in inflammation and disease is now out in the Annual Review of Immunology !
https://www.annualreviews.org/doi/full/10.1146/annurev-immunol-071719-094903

 

Atopic dermatitis: allergens are playing with your nerves !

We are thrilled to see our last study published in Nature Immunology. Congratulations to Nadine Serhan and Lilian Basso for their fantastic work selected for the cover of November issue !
https://www.nature.com/articles/s41590-019-0493-z

Lab data gallery

Photo:

Whole mouse skin 3D staining of peripheral neurons (PGP9.5 yellow) and cells nucleus (DAPI cyan)

 

 

Claudin 1 expression (red) and cells nucleus (DAPI cyan) in mouse epidermis

 

 

 

 

3D image of a human primary mast cell degranulated in a matrigel (exteriorized granules are stained using fluorochrome-labeled avidin, red)

 

 

Mouse lymph node section stained with a combination of 7 antibodies to identify different populations of immune cells. Confocal microscopy.

 

 

Modeling of substance P expression (green) and mast cell granules (red) in whole mounted skin. Confocal Microscopy and computational analysis.

 

 

Dorsal root ganglia (DRG) neurons, subtypes of neurons (red) and nucleus (DAPI, Cyan). 3D confocal microscopy.

 

 

 

Activated TRPV1+ sensory neurons (genetically-encoded calcium tracer, cyan) and degranulated mast cells (avidin, red). Intravital two-photon microscopy of mouse ear dermis.

 

 

 

Video:

 

Video 1. ​Distinc degranulation dynamics induced by anti-IgE or substance P in human primary mast cells (Intracellular calcium green, released granules red). Confocal microscopy. Gaudenzio et al. JCI 2016.
 
 
Video  2. Monitoring of mast cell granules (red) and calcium levels in sensory neurons (white color scale) in living mice injected with vehicle (left) or a TRPV1 agonist (right). Intravital two-photon microscopy of the skin.

Video  3. Monitoring of mast cell granules (red) and blood flow (green) in living mice sensitized with DNP-specific IgE and injected with vehicle. Intravital two-photon microscopy of the skin. Reber et al. JCI Insight 2017.

Video  4. Monitoring of mast cell granules (red) and blood flow (green)  mice sensitized with DNP-specific IgE and challenged with DNP-HSA. Intravital two-photon microscopy of the skin. Reber et al. JCI Insight 2017.

ERC

ERC

ATIP AVENIR

ATIP AVENIR

Marie Curie

Marie Curie

INSERM

INSERM

Société Française de Dermatologie (SFD)

Société Française de Dermatologie (SFD)

Société Française d’Allergologie (SFA)

Société Française d’Allergologie (SFA)

ARTHRITIS

ARTHRITIS