Author
Jean-François Gauchat
Bio: Jean-François Gauchat is an academic researcher from Université de Montréal. The author has contributed to research in topics: Cytokine & Glycoprotein 130. The author has an hindex of 15, co-authored 32 publications receiving 1235 citations.
Papers
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TL;DR: Results show that IL-21, in addition to promoting growth and differentiation of committed B cells, is a specific switch factor for the production of IgG1 and IgG3.
Abstract: IL-21 is a cytokine that regulates the activation of T and NK cells and promotes the proliferation of B cells activated via CD40. In this study, we show that rIL-21 strongly induces the production of all IgG isotypes by purified CD19(+) human spleen or peripheral blood B cells stimulated with anti-CD40 mAb. Moreover, it was found to specifically induce the production of IgG(1) and IgG(3) by CD40-activated CD19(+)CD27(-) naive human B cells. Although stimulation of CD19(+) B cells via CD40 alone induced gamma 1 and gamma 3 germline transcripts, as well as the expression of activation-induced cytidine deaminase, only stimulation with both anti-CD40 mAb and rIL-21 resulted in the production of S gamma/S mu switch circular DNA. These results show that IL-21, in addition to promoting growth and differentiation of committed B cells, is a specific switch factor for the production of IgG(1) and IgG(3).
301 citations
TL;DR: It is found that deficiency in signaling via type I interferon receptor led to deregulated activation of group 2 innate lymphoid cells (ILC2 cells) and infection-associated type 2 immunopathology.
Abstract: Viral respiratory tract infections are the main causative agents of the onset of infection-induced asthma and asthma exacerbations that remain mechanistically unexplained. Here we found that deficiency in signaling via type I interferon receptor led to deregulated activation of group 2 innate lymphoid cells (ILC2 cells) and infection-associated type 2 immunopathology. Type I interferons directly and negatively regulated mouse and human ILC2 cells in a manner dependent on the transcriptional activator ISGF3 that led to altered cytokine production, cell proliferation and increased cell death. In addition, interferon-γ (IFN-γ) and interleukin 27 (IL-27) altered ILC2 function dependent on the transcription factor STAT1. These results demonstrate that type I and type II interferons, together with IL-27, regulate ILC2 cells to restrict type 2 immunopathology.
272 citations
University of North Carolina at Chapel Hill1, Montreal Heart Institute2, Osaka University3, VA Boston Healthcare System4, Icahn School of Medicine at Mount Sinai5, Queen Mary University of London6, University of Cambridge7, National Institute for Health Research8, Wellcome Trust Sanger Institute9, Harvard University10, Vanderbilt University11, University of Wisconsin–Milwaukee12, Université de Montréal13, University of Southern California14, Kyushu University15, University of Washington16, University of Bristol17, University of Copenhagen18, Erasmus University Medical Center19, National Institutes of Health20, Brigham and Women's Hospital21, Kaiser Permanente22, University of Mississippi Medical Center23, International Agency for Research on Cancer24, Wake Forest University25, Imperial College London26, Broad Institute27, University of Pennsylvania28, Greifswald University Hospital29, Fred Hutchinson Cancer Research Center30, Chinese National Human Genome Center31, Technische Universität München32, University of Tampere33, University of Tokyo34, University of Ioannina35, University of Colorado Denver36, Duke University37, University of Virginia38, NHS Blood and Transplant39, University of Minnesota40, Turku University Hospital41, Los Angeles Biomedical Research Institute42, Stanford University43, King's College London44, Mashhad University of Medical Sciences45, Veterans Health Administration46
TL;DR: The clinical significance and predictive value of trans-ethnic variants in multiple populations are explored, genetic architecture and the effect of natural selection on these blood phenotypes between populations are compared and the value of a more global representation of populations in genetic studies is highlighted.
233 citations
TL;DR: CNTFR-specific mutants of CNTF have been developed that bind to the CNTFRα-LIFRβ-gp130 receptor, which may prove to be a breakthrough for therapeutic applications of systemically administered CNTF in pathologies such as multiple sclerosis or Alzheimer's disease.
101 citations
TL;DR: Results indicated that association of GPL to the intracellular portions of gp130, or LIF receptor, allowed the signaling cascade, indicating a possible involvement of GPL in Th1-type immune responses.
92 citations
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TL;DR: This review discusses recent progress and areas of uncertainty or disagreement in the literature, and debates the developmental relationship between T(FH) cells and other CD4 T cell subsets (Th1, Th2, Th17, iTreg).
Abstract: T cell help to B cells is a fundamental aspect of adaptive immunity and the generation of immunological memory. Follicular helper CD4 T (T(FH)) cells are the specialized providers of B cell help. T(FH) cells depend on expression of the master regulator transcription factor Bcl6. Distinguishing features of T(FH) cells are the expression of CXCR5, PD-1, SAP (SH2D1A), IL-21, and ICOS, among other molecules, and the absence of Blimp-1 (prdm1). T(FH) cells are important for the formation of germinal centers. Once germinal centers are formed, T(FH) cells are needed to maintain them and to regulate germinal center B cell differentiation into plasma cells and memory B cells. This review covers T(FH) differentiation, T(FH) functions, and human T(FH) cells, discussing recent progress and areas of uncertainty or disagreement in the literature, and it debates the developmental relationship between T(FH) cells and other CD4 T cell subsets (Th1, Th2, Th17, iTreg).
2,442 citations
TL;DR: In this article, human blood CXCR5(+)CD4(+) T cells share functional properties with T follicular helper (Tfh) cells and appear to represent their circulating memory compartment.
1,263 citations
Aix-Marseille University1, Cornell University2, Washington University in St. Louis3, Charité4, Pasteur Institute5, French Institute of Health and Medical Research6, Keio University7, University of California, San Francisco8, Laboratory of Molecular Biology9, VU University Amsterdam10, University of Oxford11, University of Amsterdam12
TL;DR: The advances in ILC biology over the past decade are distill the advances to refine the nomenclature of ILCs and highlight the importance of I LCs in tissue homeostasis, morphogenesis, metabolism, repair, and regeneration.
1,252 citations
TL;DR: Data indicate that IL-31 may be involved in promoting the dermatitis and epithelial responses that characterize allergic and non-allergic diseases.
Abstract: T cell–derived cytokines are important in the development of an effective immune response, but when dysregulated they can promote disease. Here we identify a four-helix bundle cytokine we have called interleukin 31 (IL-31), which is preferentially produced by T helper type 2 cells. IL-31 signals through a receptor composed of IL-31 receptor A and oncostatin M receptor. Expression of IL-31 receptor A and oncostatin M receptor mRNA was induced in activated monocytes, whereas epithelial cells expressed both mRNAs constitutively. Transgenic mice overexpressing IL-31 developed severe pruritis, alopecia and skin lesions. Furthermore, IL-31 receptor expression was increased in diseased tissues derived from an animal model of airway hypersensitivity. These data indicate that IL-31 may be involved in promoting the dermatitis and epithelial responses that characterize allergic and non-allergic diseases.
926 citations
TL;DR: This Review highlights experimental evidence from mouse models and patient-based studies that have elucidated the effects of ILCs on the maintenance of tissue homeostasis and the consequences for health and disease.
Abstract: Research over the last 7 years has led to the formal identification of innate lymphoid cells (ILCs), increased the understanding of their tissue distribution and has established essential functions of ILCs in diverse physiological processes. These include resistance to pathogens, the regulation of autoimmune inflammation, tissue remodeling, cancer and metabolic homeostasis. Notably, many ILC functions appear to be regulated by mechanisms distinct from those of other innate and adaptive immune cells. In this Review, we focus on how group 2 ILC (ILC2) and group 3 ILC (ILC3) responses are regulated and how these cells interact with other immune and non-immune cells to mediate their functions. We highlight experimental evidence from mouse models and patient-based studies that have elucidated the effects of ILCs on the maintenance of tissue homeostasis and the consequences for health and disease.
729 citations