A5025083136- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cancer Research and Treatments
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Cancer, Hypoxia, and Metabolism
- IL-33, ST2, and ILC Pathways
- Lung Cancer Research Studies
- RNA modifications and cancer
- Genetic Neurodegenerative Diseases
- Immune cells in cancer
- Genetics, Aging, and Longevity in Model Organisms
- Mitochondrial Function and Pathology
- Gut microbiota and health
- Immunotherapy and Immune Responses
- Clinical Nutrition and Gastroenterology
- Diabetes and associated disorders
- Wound Healing and Treatments
- CRISPR and Genetic Engineering
Université Paris Sciences et Lettres
2018-2024
Immunité et Cancer
2018-2024
Inserm
2010-2024
Institut Curie
2018-2024
Délégation Paris 5
2012
Université Paris Cité
2012
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,...
Abstract γδ T cells perform heterogeneous functions in homeostasis and disease across tissues. However, it is unclear whether these roles correspond to distinct subsets or a homogeneous population of exerting context-dependent functions. Here, by cross-organ multimodal single-cell profiling, we reveal that various mouse tissues harbor unique site-adapted subsets. Epidermal intestinal intraepithelial are transcriptionally exhibit epigenetic hallmarks functional diversity. Through parabiosis...
CD4+ T cell antitumor responses have mostly been studied in transplanted tumors expressing secreted model antigens (Ags), while most mutated proteins human cancers are not secreted. The fate of Ag-specific cells recognizing a cytoplasmic Ag mice bearing autochthonous is still unclear. Here we show, using genetically engineered lung adenocarcinoma mouse model, that naive tumor-specific activated and proliferate the tumor-draining lymph node (TdLN) but do differentiate into effectors or...
Although CD8+ T cells undergo autonomous clonal proliferation after antigen stimulation in vivo, the expansion of activated CD4+ is limited by intrinsic factors that are poorly characterized. Using genome-wide CRISPR-Cas9 screens and an vivo system modeling antigen-experienced cell recruitment during a localized immune response, we identified suppressor cytokine signaling 1 (SOCS1) as major nonredundant checkpoint imposing brake on proliferation. anti–interleukin-2 receptor (IL-2R) blocking...
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...
One of the current challenges neurodegenerative disease research is to determine whether signaling pathways that are essential cellular homeostasis might contribute neuronal survival and modulate pathogenic process in human disease. In Caenorhabditis elegans , sir-2.1 /SIRT1 overexpression protects neurons from early phases expanded polyglutamine (polyQ) toxicity, this protection requires longevity-promoting factor daf-16/ FOXO. Here, we show neuroprotective effect also DAF-16/FOXO partner...
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....
Abstract One billion people worldwide get flu every year, including patients with non–small cell lung cancer (NSCLC). However, the impact of acute influenza A virus (IAV) infection on composition tumor microenvironment (TME) and clinical outcome NSCLC is largely unknown. We set out to understand how IAV load impacts growth modifies cellular molecular players in TME. Herein, we report that can infect both immune cells, resulting a long-term protumoral effect tumor-bearing mice....
Summary The expansion of antigen experienced CD4 + T cells is limited by intrinsic factors. Using in vivo genome-wide CRISPR-Cas9 screens, we identified SOCS1 as a non-redundant checkpoint imposing brake on T-cell proliferation upon rechallenge. We show here that critical node integrating both IL-2 and IFN-γ signals blocking multiple signaling pathways to abrogate Th1 cell response. In CD8 T-cell, does not impact the but rather reduces survival effector functions. By targeting SOCS1, murine...
<p>Supplementary data file</p>
<div>Abstract<p>One billion people worldwide get flu every year, including patients with non–small cell lung cancer (NSCLC). However, the impact of acute influenza A virus (IAV) infection on composition tumor microenvironment (TME) and clinical outcome NSCLC is largely unknown. We set out to understand how IAV load impacts growth modifies cellular molecular players in TME. Herein, we report that can infect both immune cells, resulting a long-term protumoral effect tumor-bearing...
<div>Abstract<p>One billion people worldwide get flu every year, including patients with non–small cell lung cancer (NSCLC). However, the impact of acute influenza A virus (IAV) infection on composition tumor microenvironment (TME) and clinical outcome NSCLC is largely unknown. We set out to understand how IAV load impacts growth modifies cellular molecular players in TME. Herein, we report that can infect both immune cells, resulting a long-term protumoral effect tumor-bearing...
<p>Supplementary data file</p>
<p>Supplementary data file</p>
<p>Supplementary data file</p>
<div>Abstract<p>One billion people worldwide get flu every year, including patients with non–small cell lung cancer (NSCLC). However, the impact of acute influenza A virus (IAV) infection on composition tumor microenvironment (TME) and clinical outcome NSCLC is largely unknown. We set out to understand how IAV load impacts growth modifies cellular molecular players in TME. Herein, we report that can infect both immune cells, resulting a long-term protumoral effect tumor-bearing...
Generating knockout mice for target molecules in specific T cell populations, without subset-specific promoters, is time-consuming and costly. Here, we describe steps enriching mucosal-associated invariant cells from the thymus, expanding them vitro performing a CRISPR-Cas9 knockout. We then detail procedure injecting into wounded Cd3ε−/− characterizing skin. For complete details on use execution of this protocol, please refer to du Halgouet et al. (2023).1
Abstract Epithelial repair is crucial to reestablish adequate barrier integrity and function after tissue injury. In both mice humans, MAIT (Mucosal associated invariant T) cells involvement in substantiated by their upregulation of mediators following TCR-mediated activation. Additionally, the absence ɣδT cells, were shown promote wound healing. By using our congenic B6-MAIT CASTstrain (10× more than B6 mice) a skin excision mouse model preventing epithelial contraction (mimicking human...
<h3>Background</h3> The FOXO longevity pathway and β-catenin are major signalling systems that may regulate cell survival. Whether GSK3/β-catenin interact with to diseased neuron survival whether this translate into the modification of human neurodegenerative disease remain unknown. <h3>Aims</h3> We aimed test role neighbours such as on effects expanded polyQs/mutant huntingtin. <h3>Methods</h3> used complementary approaches based a <i>C elegans</i> model neuronal dysfunction induced by...
<h3>Background</h3> Huntington9s disease (HD) is a neurodegenerative pathology induced by cell toxicity caused polyglutamine (polyQ) expansion in the N terminal end of huntingtin (htt). Using <i>C elegans</i> transgenics that express expanded polyQs neurons, we identified gene network centred onto FoxO and protects neurons from screen for genes modulate early phases polyQ neurotoxicity. Among these genes, AMPK, well known energy sensor involved lifespan health span extension worms mammals....