A5039944847- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- IL-33, ST2, and ILC Pathways
- CAR-T cell therapy research
- Gut microbiota and health
- Cytomegalovirus and herpesvirus research
- Sphingolipid Metabolism and Signaling
- Eicosanoids and Hypertension Pharmacology
- Cancer Immunotherapy and Biomarkers
- Glutathione Transferases and Polymorphisms
- Effects of Radiation Exposure
- Diabetes and associated disorders
- Neuropeptides and Animal Physiology
- Hepatitis C virus research
- Endoplasmic Reticulum Stress and Disease
- Phagocytosis and Immune Regulation
- Bacillus and Francisella bacterial research
- vaccines and immunoinformatics approaches
- Viral gastroenteritis research and epidemiology
- Clostridium difficile and Clostridium perfringens research
- Escherichia coli research studies
- Inflammatory mediators and NSAID effects
- Clinical Nutrition and Gastroenterology
- Polyomavirus and related diseases
Inserm
2013-2024
Université Paris Sciences et Lettres
2017-2024
Institut Curie
2016-2024
Institut de génétique et de développement de Rennes
2022-2024
Centre National de la Recherche Scientifique
2022-2024
Université de Rennes
2022-2024
Immunité et Cancer
2023-2024
Massachusetts General Hospital
2012-2019
Harvard University
2012-2019
Zero to Three
2019
Commensals rule the MAITrix Mucosal-associated invariant T (MAIT) cells play an important role in mucosal homeostasis. MAIT recognize microbial small molecules presented by major histocompatibility complex class Ib molecule MR1. are absent germ-free mice, and mechanisms which microbiota control cell development unknown (see Perspective Oh Unutmaz). Legoux et al. show that, of within thymus is governed bacterial product 5-(2-oxopropylideneamino)-6- d -ribitylaminouracil, rapidly traffics from...
Mucosal-associated invariant T (MAIT) cells are abundant with unique specificity for microbial metabolites. MAIT conservation along evolution indicates important functions, but their low frequency in mice has hampered detailed characterization. Here, we performed the first transcriptomic analysis of murine cells. MAIT1 (RORγtneg) and MAIT17 (RORγt+) subsets were markedly distinct from mainstream cells, quasi-identical to NKT1 NKT17 subsets. The expression similar programs was further...
Tissue repair processes maintain proper organ function following mechanical or infection-related damage. In addition to antibacterial properties, mucosal associated invariant T (MAIT) cells express a tissue transcriptomic program and promote skin wound healing when expanded. Herein, we use human-like mouse model of full-thickness excision assess the underlying mechanisms MAIT cell function. Single-cell RNA sequencing analysis suggested that already at steady state. Following excision,...
Protective T cell responses elicited along chronic human CMV (HCMV) infections are sometimes dominated by CD8 clones bearing highly related or identical public TCR in unrelated individuals. To understand the principles that guide emergence of these responses, we have performed structural, biophysical, and functional analyses an immunodominant (RA14) directed against a major HLA-A*0201-restricted HCMV Ag (pp65(495-503)) selected vivo from diverse repertoire after stimulations. Unlike two TCRs...
Mucosal-associated invariant T (MAIT) cells harbor evolutionarily conserved TCRs, suggesting important functions. As human and mouse MAIT functional programs appear distinct, the features remain unidentified. Using species-specific tetramers coupled to single-cell RNA sequencing, we characterized cell development in six species spanning 110 million years of evolution. Cross-species analyses revealed transcriptional events underlying maturation, marked by ZBTB16 induction all species. human,...
Intestinal inflammation shifts microbiota composition and metabolism. How the host monitors responds to such changes remains unclear. Here, we describe a protective mechanism by which mucosal-associated invariant T (MAIT) cells detect metabolites produced upon intestinal promote tissue repair. At steady state, MAIT ligands derived from riboflavin biosynthesis pathway were aerotolerant bacteria residing in colonic mucosa. Experimental colitis triggered luminal expansion of...
A previous in vitro study showed that sphingosine-1-phosphate (S1P), a ceramide antagonist, preserved endothelial cells culture from radiation-induced apoptosis. We proposed to validate the role of S1P tissue radioprotection by inhibiting acute gastrointestinal (GI) syndrome induced cell apoptosis after high dose radiation. Retro-orbital was injected mice exposed 15 Gy, dose-inducing GI within 10 days. Overall survival and on intestines sections were studied. Intestinal type targeted early...
The impact of MHC phenotype on the shaping peripheral naive T cell repertoire in humans remains unknown. To address this, we compared frequency and antigenic avidity cells specific for immunodominant self-, viral, tumor Ags presented by a human class I allele (HLA-A*02, referred to as A2) individuals expressing or not this allele. Naive frequencies varied from one Ag specificity another but were restrained given specificity. Although A2-restricted showed similar features avidities A2+ A2-...
A basic necessity for researchers studying adaptive immunity with in vivo experimental models is an ability to identify T cells based on their cell antigen receptor (TCR) specificity. Many indirect methods are available which a bulk population of stimulated vitro specific and epitope-specific identified through the measurement functional response such as proliferation, cytokine production, or expression activation markers(1). However, these only exhibiting one many possible functions, they...
The structural rules governing peptide/MHC (pMHC) recognition by T cells remain unclear. To address this question, we performed a characterization of several HLA-A2/peptide complexes and assessed in parallel their antigenicity, analyzing the frequency corresponding Ag-specific naive A2(+) A2(-) individuals, as well within CD4(+) CD8(+) subsets. We were able to find correlation between specific cell peptide solvent accessibility and/or mobility for subset moderately prominent peptides....
How T-cell receptor (TCR) characteristics determine subset commitment during development is still unclear. Here, we addressed this question for innate-like T cells, mucosal-associated invariant (MAIT) and natural killer (iNKT) cells. MAIT iNKT cells have similar developmental paths, leading in mice to two effector subsets, cytotoxic (MAIT1/iNKT1) IL17-secreting (MAIT17/iNKT17). For iNKT1 vs iNKT17 fate choice, an instructive role TCR affinity was proposed but recent data argue against model....
Intracellular pathogens lose many metabolic genes during their evolution from free-living bacteria, but the pathogenic consequences of altered programs on host immunity are poorly understood. Here, we show that a strain Francisella tularensis subsp. (FT) has five amino acid substitutions in RibD, converting enzyme riboflavin synthetic pathway responsible for generating metabolites recognized by mucosal-associated invariant T (MAIT) cells. Metabolites strain, F. novicida (FN), activated MAIT...
In the thymus, a T‐cell repertoire able to confer protection against infectious and noninfectious agents in peptide‐dependent, self‐MHC‐restricted manner is selected. Direct detection of Ag‐specific thymocytes, analysis impact expression MHC‐restricting allele on their frequency or function has never been studied humans because extremely low precursor frequency. Here, we used tetramer‐based enrichment protocol analyze ex vivo activation‐phenotype human thymocytes specific for self, viral...
A basic necessity for researchers studying adaptive immunity with in vivo experimental models is an ability to identify T cells based on their cell antigen receptor (TCR) specificity. Many indirect methods are available which a bulk population of stimulated vitro specific and epitope-specific identified through the measurement functional response such as proliferation, cytokine production, or expression activation markers1. However, these only exhibiting one many possible functions, they not...
While CD4(+) T lymphocytes usually recognize antigens in the context of major histocompatibility (MHC) class II alleles, occurrence MHC class-I restricted cells has been reported sporadically. Taking advantage a highly sensitive tetramer-based enrichment approach allowing detection and isolation scarce Ag-specific cells, we performed systematic comparative analysis HLA-A*0201-restricted CD8(+) T-cell lines directed against several immunodominant viral or tumoral antigens. every peptide-MHC I...