@article{lacouture_lfa-1_2024,

title = {LFA-1 nanoclusters integrate TCR stimulation strength to tune T-cell cytotoxic activity},

author = {Claire Lacouture and Beatriz Chaves and Delphine Guipouy and Raïssa Houmadi and Valérie Duplan-Eche and Sophie Allart and Nicolas Destainville and Loïc Dupré},

url = {https://www.nature.com/articles/s41467-024-44688-3},

doi = {10.1038/s41467-024-44688-3},

issn = {2041-1723},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {Nature Communications},

volume = {15},

number = {1},

pages = {407},

abstract = {T-cell cytotoxic function relies on the cooperation between the highly specific but poorly adhesive T-cell receptor (TCR) and the integrin LFA-1. How LFA-1-mediated adhesion may scale with TCR stimulation strength is ill-defined. Here, we show that LFA-1 conformation activation scales with TCR stimulation to calibrate human T-cell cytotoxicity. Super-resolution microscopy analysis reveals that >1000 LFA-1 nanoclusters provide a discretized platform at the immunological synapse to translate TCR engagement and density of the LFA-1 ligand ICAM-1 into graded adhesion. Indeed, the number of high-affinity conformation LFA-1 nanoclusters increases as a function of TCR triggering strength. Blockade of LFA-1 conformational activation impairs adhesion to target cells and killing. However, it occurs at a lower TCR stimulation threshold than lytic granule exocytosis implying that it licenses, rather than directly controls, the killing decision. We conclude that the organization of LFA-1 into nanoclusters provides a calibrated system to adjust T-cell killing to the antigen stimulation strength.},

note = {Number: 1 

Publisher: Nature Publishing Group},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Malnou2023,

title = {Editorial: Recent highlights in the development of therapeutic antiviral strategies},

author = {Cécile E. Malnou and Gaëtan Ligat},

doi = {10.3389/fmicb.2023.1338999},

issn = {1664-302X},

year  = {2023},

date = {2023-12-05},

urldate = {2023-12-05},

journal = {Front. Microbiol.},

volume = {14},

publisher = {Frontiers Media SA},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@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{pmid37748654,

title = {Widespread monoclonal IgE antibody convergence to an immunodominant, proanaphylactic Ara h 2 epitope in peanut allergy},

author = {Derek Croote and Joyce J W Wong and Cyprien Pecalvel and Edouard Leveque and Natacha Casanovas and Jasper B J Kamphuis and Paige Creeks and Johanna Romero and Saba Sohail and Daniel Bedinger and Kari C Nadeau and Rebecca S Chinthrajah and Laurent L Reber and Henry B Lowman},

doi = {10.1016/j.jaci.2023.08.035},

issn = {1097-6825},

year  = {2023},

date = {2023-09-01},

urldate = {2023-09-01},

journal = {J Allergy Clin Immunol},

abstract = {BACKGROUND: Despite their central role in peanut allergy, human monoclonal IgE antibodies have eluded characterization.nnOBJECTIVE: We sought to define the sequences, affinities, clonality, and functional properties of human monoclonal IgE antibodies in peanut allergy.nnMETHODS: We applied our single-cell RNA sequencing-based SEQ SIFTER discovery platform to samples from allergic individuals who varied by age, sex, ethnicity, and geographic location in order to understand commonalities in the human IgE response to peanut allergens. Select antibodies were then recombinantly expressed and characterized for their allergen and epitope specificity, affinity, and functional properties.nnRESULTS: We found striking convergent evolution of IgE monoclonal antibodies (mAbs) from several clonal families comprising both memory B cells and plasmablasts. These antibodies bound with subnanomolar affinity to the immunodominant peanut allergen Ara h 2, specifically a linear, repetitive motif. Further characterization of these mAbs revealed their ability to single-handedly cause affinity-dependent degranulation of human mast cells and systemic anaphylaxis on peanut allergen challenge in humanized mice. Finally, we demonstrated that these mAbs, reengineered as IgGs, inhibit significant, but variable, amounts of Ara h 2- and peanut-mediated degranulation of mast cells sensitized with allergic plasma.nnCONCLUSIONS: Convergent evolution of IgE mAbs in peanut allergy is a common phenomenon that can reveal immunodominant epitopes on major allergenic proteins. Understanding the functional properties of these molecules is key to developing therapeutics, such as competitive IgG inhibitors, that are able to stoichiometrically outcompete endogenous IgE for allergen and thereby prevent allergic cascade in cases of accidental allergen exposure.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37697719,

title = {Single-cell RNA sequencing identifies senescence as therapeutic target in rhabdomyolysis-induced acute kidney injury},

author = {Snigdha N Rao and Margot Zahm and Audrey Casemayou and Marie Buleon and Stanislas Faguer and Guylène Feuillet and Jason S Iacovoni and Olivier P Joffre and Ignacio Gonzalez-Fuentes and Emeline Lhuillier and Frédéric Martins and Elodie Riant and Alexia Zakaroff-Girard and Joost P Schanstra and Jean Sébastien Saulnier Blache and Julie Belliere},

doi = {10.1093/ndt/gfad199},

issn = {1460-2385},

year  = {2023},

date = {2023-09-01},

urldate = {2023-09-01},

journal = {Nephrol Dial Transplant},

abstract = {BACKGROUND: The role of macrophages in the development of rhabdomyolysis induced acute kidney injury (RM-AKI) has been established, but an in-depth understanding of the changes in the immune landscape could help to improve targeted strategies. Whereas senescence is usually associated with chronic kidney processes, we also wished to explore whether senescence could also occur in AKI and whether senolytics could act on immune cells.nnMETHODS: Single-cell RNA sequencing was used in the murine glycerol-induced RM-AKI model to dissect the transcriptomic characteristics of CD45+ live cells sorted from kidneys 2 days after injury. Public datasets from murine AKI models were reanalyzed to explore cellular senescence signature in tubular epithelial cells (TECs). A combination of senolytics (dasatinib and quercetin, DQ) was administered to mice exposed or not to RM-AKI.nnRESULTS: Unsupervised clustering of nearly 17,000 single-cell transcriptomes identified 7 known immune cell clusters. Sub-clustering of the mononuclear phagocyte cells (MPC), revealed 9 distinct cell sub-populations differently modified with RM. One macrophage cluster was particularly interesting since it behaved as a critical node in a trajectory connecting one MCHIIhigh cluster only present in control to 2 MCHIIlow clusters only present in RM-AKI. This critical cluster expressed a senescence gene signature, that was very different from that of the TECs. Senolytic DQ treatment blocked the switch from a F4/80highCD11blow to F4/80lowCD11bhigh phenotype, which correlated with prolonged nephroprotection in RM-AKI.nnCONCLUSIONS: scRNASeq unmasked novel transitional macrophage subpopulation associated with RM-AKI characterized by the activation of cellular senescence processes. This work provides a proof-of-concept that senolytics nephroprotective effects may rely, at least in part, on subtle immune modulation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Martin2023,

title = {The Yin and the Yang of extracellular vesicles during viral infections},

author = {Charlène Martin and Gaëtan Ligat and Cécile E. Malnou},

doi = {10.1016/j.bj.2023.100659},

issn = {2319-4170},

year  = {2023},

date = {2023-09-00},

urldate = {2023-09-00},

journal = {Biomedical Journal},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Osma-Garcia2023b,

title = {The RNA binding proteins TIA1 and TIAL1 promote Mcl1 mRNA translation to protect germinal center responses from apoptosis},

author = {Osma-Garcia, Ines C. 

and Mouysset, Mailys 

and Capitan-Sobrino, Dunja 

and Aubert, Yann 

and Turner, Martin 

and Diaz-Mu{ñ}oz, Manuel D.},

url = {https://doi.org/10.1038/s41423-023-01063-4},

doi = {10.1038/s41423-023-01063-4},

issn = {2042-0226},

year  = {2023},

date = {2023-07-20},

urldate = {2023-07-20},

journal = {Cellular & Molecular Immunology},

abstract = {Germinal centers (GCs) are essential for the establishment of long-lasting antibody responses. GC B cells rely on post-transcriptional RNA mechanisms to translate activation-associated transcriptional programs into functional changes in the cell proteome. However, the critical proteins driving these key mechanisms are still unknown. Here, we show that the RNA binding proteins TIA1 and TIAL1 are required for the generation of long-lasting GC responses. TIA1- and TIAL1-deficient GC B cells fail to undergo antigen-mediated positive selection, expansion and differentiation into B-cell clones producing high-affinity antibodies. Mechanistically, TIA1 and TIAL1 control the transcriptional identity of dark- and light-zone GC B cells and enable timely expression of the prosurvival molecule MCL1. Thus, we demonstrate here that TIA1 and TIAL1 are key players in the post-transcriptional program that selects high-affinity antigen-specific GC B cells.},

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{pmid37012202,

title = {C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress-Induced Ferroptosis in FLT3-Mutant Leukemia},

author = {Marie Sabatier and Rudy Birsen and Laura Lauture and Sarah Mouche and Paolo Angelino and Jonas Dehairs and Léa Goupille and Ismael Boussaid and Maël Heiblig and Emeline Boet and Ambrine Sahal and Estelle Saland and Juliana C Santos and Marc Armengol and Miranda Fernández-Serrano and Thomas Farge and Guillaume Cognet and Federico Simonetta and Corentin Pignon and Antoine Graffeuil and Céline Mazzotti and Hervé Avet-Loiseau and Océane Delos and Justine Bertrand-Michel and Amélie Chedru and Vilma Dembitz and Paolo Gallipoli and Natasha S Anstee and Sun Loo and Andrew H Wei and Martin Carroll and Armelle Goubard and Rémy Castellano and Yves Collette and François Vergez and Véronique Mansat-De Mas and Sarah Bertoli and Suzanne Tavitian and Muriel Picard and Christian Récher and Nathalie Bourges-Abella and Fanny Granat and Olivier Kosmider and Pierre Sujobert and Benoit Colsch and Carine Joffre and Lucille Stuani and Johannes V Swinnen and Hervé Guillou and Gael Roué and Nawad Hakim and Anne S Dejean and Petros Tsantoulis and Clément Larrue and Didier Bouscary and Jerome Tamburini and Jean-Emmanuel Sarry},

doi = {10.1158/2159-8290.CD-22-0411},

issn = {2159-8290},

year  = {2023},

date = {2023-07-01},

urldate = {2023-07-01},

journal = {Cancer Discov},

volume = {13},

number = {7},

pages = {1720--1747},

abstract = {Although transcription factor CCAAT-enhancer binding protein α (C/EBPα) is critical for normal and leukemic differentiation, its role in cell and metabolic homeostasis is largely unknown in cancer. Here, multiomics analyses uncovered a coordinated activation of C/EBPα and Fms-like tyrosine kinase 3 (FLT3) that increased lipid anabolism in vivo and in patients with FLT3-mutant acute myeloid leukemia (AML). Mechanistically, C/EBPα regulated the fatty acid synthase (FASN)-stearoyl-CoA desaturase (SCD) axis to promote fatty acid (FA) biosynthesis and desaturation. We further demonstrated that FLT3 or C/EBPα inactivation decreased monounsaturated FA incorporation to membrane phospholipids through SCD downregulation. Consequently, SCD inhibition enhanced susceptibility to lipid redox stress that was exploited by combining FLT3 and glutathione peroxidase 4 inhibition to trigger lipid oxidative stress, enhancing ferroptotic death of FLT3-mutant AML cells. Altogether, our study reveals a C/EBPα function in lipid homeostasis and adaptation to redox stress, and a previously unreported vulnerability of FLT3-mutant AML to ferroptosis with promising therapeutic application.nnSIGNIFICANCE: FLT3 mutations are found in 30% of AML cases and are actionable by tyrosine kinase inhibitors. Here, we discovered that C/EBPα regulates FA biosynthesis and protection from lipid redox stress downstream mutant-FLT3 signaling, which confers a vulnerability to ferroptosis upon FLT3 inhibition with therapeutic potential in AML. This article is highlighted in the In This Issue feature, p. 1501.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37080596,

title = {Effects of a Small-Molecule Perforin Inhibitor in a Mouse Model of CD8 T Cell-Mediated Neuroinflammation},

author = {Carmen Gonzalez-Fierro and Coralie Fonte and Eloïse Dufourd and Vincent Cazaentre and Sidar Aydin and Britta Engelhardt and Rachel R Caspi and Biying Xu and Guillaume Martin-Blondel and Julie A Spicer and Joseph A Trapani and Jan Bauer and Roland S Liblau and Chloé Bost},

doi = {10.1212/NXI.0000000000200117},

issn = {2332-7812},

year  = {2023},

date = {2023-07-01},

urldate = {2023-07-01},

journal = {Neurol Neuroimmunol Neuroinflamm},

volume = {10},

number = {4},

abstract = {BACKGROUND AND OBJECTIVES: Alteration of the blood-brain barrier (BBB) at the interface between blood and CNS parenchyma is prominent in most neuroinflammatory diseases. In several neurologic diseases, including cerebral malaria and Susac syndrome, a CD8 T cell-mediated targeting of endothelial cells of the BBB (BBB-ECs) has been implicated in pathogenesis.nnMETHODS: In this study, we used an experimental mouse model to evaluate the ability of a small-molecule perforin inhibitor to prevent neuroinflammation resulting from cytotoxic CD8 T cell-mediated damage of BBB-ECs.nnRESULTS: Using an in vitro coculture system, we first identified perforin as an essential molecule for killing of BBB-ECs by CD8 T cells. We then found that short-term pharmacologic inhibition of perforin commencing after disease onset restored motor function and inhibited the neuropathology. Perforin inhibition resulted in preserved BBB-EC viability, maintenance of the BBB, and reduced CD8 T-cell accumulation in the brain and retina.nnDISCUSSION: Therefore, perforin-dependent cytotoxicity plays a key role in the death of BBB-ECs inflicted by autoreactive CD8 T cells in a preclinical model and potentially represents a therapeutic target for CD8 T cell-mediated neuroinflammatory diseases, such as cerebral malaria and Susac syndrome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37236806,

title = {Immunohistologic Features of Cerebral Venous Thrombosis Due to Vaccine-Induced Immune Thrombotic Thrombocytopenia},

author = {Thomas Geeraerts and Céline Guilbeau-Frugier and Cédric Garcia and Vincent Memier and Nicolas Raposo and Fabrice Bonneville and Céline Gales and Jean Darcourt and Sophie Voisin and Agnès Ribes and Marie Piel-Julian and Fanny Bounes and Jean François Albucher and Franck-Emmanuel Roux and Jacques Izopet and Norbert Telmon and Jean Marc Olivot and Pierre Sié and Jan Bauer and Bernard Payrastre and Roland S Liblau},

doi = {10.1212/NXI.0000000000200127},

issn = {2332-7812},

year  = {2023},

date = {2023-07-01},

urldate = {2023-07-01},

journal = {Neurol Neuroimmunol Neuroinflamm},

volume = {10},

number = {4},

abstract = {OBJECTIVES: Vaccine-induced immune thrombotic thrombocytopenia (VITT), a recently described entity characterized by thrombosis at unusual locations such as cerebral venous sinus and splanchnic vein, has been rarely described after adenoviral-encoded COVID-19 vaccines. In this study, we report the immunohistological correlates in 3 fatal cases of cerebral venous thrombosis related to VITT analyzed at an academic medical center.nnMETHODS: Detailed neuropathologic studies were performed in 3 cases of cerebral venous thrombosis related to VITT after adenoviral COVID-19 vaccination.nnRESULTS: Autopsy revealed extensive cerebral vein thrombosis in all 3 cases. Polarized thrombi were observed with a high density of neutrophils in the core and a low density in the tail. Endothelial cells adjacent to the thrombus were largely destroyed. Markers of neutrophil extracellular trap and complement activation were present at the border and within the cerebral vein thrombi. SARS-CoV-2 spike protein was detected within the thrombus and in the adjacent vessel wall.nnDISCUSSION: Data indicate that neutrophils and complement activation associated with antispike immunity triggered by the vaccine is probably involved in the disease process.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37400646,

title = {The immunopathogenesis of narcolepsy type 1},

author = {Roland S Liblau and Daniela Latorre and Birgitte R Kornum and Yves Dauvilliers and Emmanuel J Mignot},

doi = {10.1038/s41577-023-00902-9},

issn = {1474-1741},

year  = {2023},

date = {2023-07-01},

urldate = {2023-07-01},

journal = {Nat Rev Immunol},

abstract = {Narcolepsy type 1 (NT1) is a chronic sleep disorder resulting from the loss of a small population of hypothalamic neurons that produce wake-promoting hypocretin (HCRT; also known as orexin) peptides. An immune-mediated pathology for NT1 has long been suspected given its exceptionally tight association with the MHC class II allele HLA-DQB1*06:02, as well as recent genetic evidence showing associations with polymorphisms of T cell receptor genes and other immune-relevant loci and the increased incidence of NT1 that has been observed after vaccination with the influenza vaccine Pandemrix. The search for both self-antigens and foreign antigens recognized by the pathogenic T cell response in NT1 is ongoing. Increased T cell reactivity against HCRT has been consistently reported in patients with NT1, but data demonstrating a primary role for T cells in neuronal destruction are currently lacking. Animal models are providing clues regarding the roles of autoreactive CD4 and CD8 T cells in the disease. Elucidation of the pathogenesis of NT1 will allow for the development of targeted immunotherapies at disease onset and could serve as a model for other immune-mediated neurological diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pichler2023b,

title = {TCR-independent CD137 (4-1BB) signaling promotes CD8+-exhausted T cell proliferation and terminal differentiation},

author = {Andrea C. Pichler and Nadège Carrié and Marine Cuisinier and Samira Ghazali and Allison Voisin and Pierre-Paul Axisa and Marie Tosolini and Céline Mazzotti and Dominic P. Golec and Sabrina Maheo and Laura do Souto and Rüçhan Ekren and Eve Blanquart and Lea Lemaitre and Virginie Feliu and Marie-Véronique Joubert and Jennifer L. Cannons and Camille Guillerey and Hervé Avet-Loiseau and Tania H. Watts and Benoit L. Salomon and Olivier Joffre and Yenkel Grinberg-Bleyer and Pamela L. Schwartzberg and Liliana E. Lucca and Ludovic Martinet},

doi = {10.1016/j.immuni.2023.06.007},

issn = {1074-7613},

year  = {2023},

date = {2023-07-00},

journal = {Immunity},

volume = {56},

number = {7},

pages = {1631--1648.e10},

publisher = {Elsevier BV},

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{block_systemic_2023,

title = {Systemic Inflammation and Normocytic Anemia in DOCK11 Deficiency},

author = {Block, Jana and Rashkova, Christina and Castanon, Irinka and Zoghi, Samaneh and Platon, Jessica and Ardy, Rico C. and Fujiwara, Mitsuhiro and Chaves, Beatriz and Schoppmeyer, Rouven and van der Made, Caspar I. and Jimenez Heredia, Raul and Harms, Frederike L. and Alavi, Samin and Alsina, Laia and Sanchez Moreno, Paula and Ávila Polo, Rainiero and Cabrera-Pérez, Rocío and Kostel Bal, Sevgi and Pfajfer, Laurène and Ransmayr, Bernhard and Mautner, Anna-Katharina and Kondo, Ryohei and Tinnacher, Anna and Caldera, Michael and Schuster, Michael and Domínguez Conde, Cecilia and Platzer, René and Salzer, Elisabeth and Boyer, Thomas and Brunner, Han G. and Nooitgedagt-Frons, Judith E. and Iglesias, Estíbaliz and Deyà-Martinez, Angela and Camacho-Lovillo, Marisol and Menche, Jörg and Bock, Christoph and Huppa, Johannes B. and Pickl, Winfried F. and Distel, Martin and Yoder, Jeffrey A. and Traver, David and Engelhardt, Karin R. and Linden, Tobias and Kager, Leo and Hannich, J. Thomas and Hoischen, Alexander and Hambleton, Sophie and Illsinger, Sabine and Da Costa, Lydie and Kutsche, Kerstin and Chavoshzadeh, Zahra and van Buul, Jaap D. and Antón, Jordi and Calzada-Hernández, Joan and Neth, Olaf and Viaud, Julien and Nishikimi, Akihiko and Dupré, Loïc and Boztug, Kaan},

doi = {10.1056/NEJMoa2210054},

issn = {1533-4406},

year  = {2023},

date = {2023-06-01},

journal = {N Engl J Med},

abstract = {BACKGROUND: Increasing evidence links genetic defects affecting actin-regulatory proteins to diseases with severe autoimmunity and autoinflammation, yet the underlying molecular mechanisms are poorly understood. Dedicator of cytokinesis 11 (DOCK11) activates the small Rho guanosine triphosphatase (GTPase) cell division cycle 42 (CDC42), a central regulator of actin cytoskeleton dynamics. The role of DOCK11 in human immune-cell function and disease remains unknown. 

METHODS: We conducted genetic, immunologic, and molecular assays in four patients from four unrelated families who presented with infections, early-onset severe immune dysregulation, normocytic anemia of variable severity associated with anisopoikilocytosis, and developmental delay. Functional assays were performed in patient-derived cells, as well as in mouse and zebrafish models. 

RESULTS: We identified rare, X-linked germline mutations in DOCK11 in the patients, leading to a loss of protein expression in two patients and impaired CDC42 activation in all four patients. Patient-derived T cells did not form filopodia and showed abnormal migration. In addition, the patient-derived T cells, as well as the T cells from Dock11-knockout mice, showed overt activation and production of proinflammatory cytokines that were associated with an increased degree of nuclear translocation of nuclear factor of activated T cell 1 (NFATc1). Anemia and aberrant erythrocyte morphologic features were recapitulated in a newly generated dock11-knockout zebrafish model, and anemia was amenable to rescue on ectopic expression of constitutively active CDC42. 

CONCLUSIONS: Germline hemizygous loss-of-function mutations affecting the actin regulator DOCK11 were shown to cause a previously unknown inborn error of hematopoiesis and immunity characterized by severe immune dysregulation and systemic inflammation, recurrent infections, and anemia. (Funded by the European Research Council and others.).},

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{pmid37126681,

title = {Epigenetic silencing of selected hypothalamic neuropeptides in narcolepsy with cataplexy},

author = {Ali Seifinejad and Mergim Ramosaj and Ling Shan and Sha Li and Marie-Laure Possovre and Corinne Pfister and Rolf Fronczek and Lee A Garrett-Sinha and David Frieser and Makoto Honda and Yoan Arribat and Dogan Grepper and Francesca Amati and Marie Picot and Andrea Agnoletto and Christian Iseli and Nicolas Chartrel and Roland Liblau and Gert J Lammers and Anne Vassalli and Mehdi Tafti},

doi = {10.1073/pnas.2220911120},

issn = {1091-6490},

year  = {2023},

date = {2023-05-01},

urldate = {2023-05-01},

journal = {Proc Natl Acad Sci U S A},

volume = {120},

number = {19},

pages = {e2220911120},

abstract = {Narcolepsy with cataplexy is a sleep disorder caused by deficiency in the hypothalamic neuropeptide hypocretin/orexin (HCRT), unanimously believed to result from autoimmune destruction of hypocretin-producing neurons. HCRT deficiency can also occur in secondary forms of narcolepsy and be only temporary, suggesting it can occur without irreversible neuronal loss. The recent discovery that narcolepsy patients also show loss of hypothalamic (corticotropin-releasing hormone) CRH-producing neurons suggests that other mechanisms than cell-specific autoimmune attack, are involved. Here, we identify the HCRT cell-colocalized neuropeptide QRFP as the best marker of HCRT neurons. We show that if HCRT neurons are ablated in mice, in addition to   transcript is also lost in the lateral hypothalamus, while in mice where only the  gene is inactivated  is unchanged. Similarly, postmortem hypothalamic tissues of narcolepsy patients show preserved  expression, suggesting the neurons are present but fail to actively produce HCRT. We show that the promoter of the  gene of patients exhibits hypermethylation at a methylation-sensitive and evolutionary-conserved PAX5:ETS1 transcription factor-binding site, suggesting the gene is subject to transcriptional silencing. We show also that in addition to HCRT,  and Dynorphin () gene promoters, exhibit hypermethylation in the hypothalamus of patients. Altogether, we propose that , , and  are epigenetically silenced by a hypothalamic assault (inflammation) in narcolepsy patients, without concurrent cell death. Since methylation is reversible, our findings open the prospect of reversing or curing narcolepsy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37253744,

title = {Antigen recognition detains CD8 T cells at the blood-brain barrier and contributes to its breakdown},

author = {Sidar Aydin and Javier Pareja and Vivianne M Schallenberg and Armelle Klopstein and Thomas Gruber and Nicolas Page and Elisa Bouillet and Nicolas Blanchard and Roland Liblau and Jakob Körbelin and Markus Schwaninger and Aaron J Johnson and Mirjam Schenk and Urban Deutsch and Doron Merkler and Britta Engelhardt},

doi = {10.1038/s41467-023-38703-2},

issn = {2041-1723},

year  = {2023},

date = {2023-05-01},

urldate = {2023-05-01},

journal = {Nat Commun},

volume = {14},

number = {1},

pages = {3106},

abstract = {Blood-brain barrier (BBB) breakdown and immune cell infiltration into the central nervous system (CNS) are early hallmarks of multiple sclerosis (MS). High numbers of CD8 T cells are found in MS lesions, and antigen (Ag) presentation at the BBB has been proposed to promote CD8 T cell entry into the CNS. Here, we show that brain endothelial cells process and cross-present Ag, leading to effector CD8 T cell differentiation. Under physiological flow in vitro, endothelial Ag presentation prevented CD8 T cell crawling and diapedesis resulting in brain endothelial cell apoptosis and BBB breakdown. Brain endothelial Ag presentation in vivo was limited due to Ag uptake by CNS-resident macrophages but still reduced motility of Ag-specific CD8 T cells within CNS microvessels. MHC class I-restricted Ag presentation at the BBB during neuroinflammation thus prohibits CD8 T cell entry into the CNS and triggers CD8 T cell-mediated focal BBB breakdown.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{36883943,

title = {Parasitic Infections and Biological Therapies Targeting Type 2 Inflammation: A VigiBase Study},

author = {Lifar P and Montastruc F and Reber LL and Magnaval JF and Guilleminault L},

url = {https://pubmed.ncbi.nlm.nih.gov/36883943/},

doi = { 10.1164/rccm.202210-1898LE},

year  = {2023},

date = {2023-05-01},

keywords = {},

pubstate = {published},

tppubtype = {article}

}