Equipe d’Accueil : Equipe 13 « Microbiote, Intestin et Inflammation »
Intitulé de l’Unité : CRSA (Centre de Recherche de Saint-Antoine), UMRS 938
Nom du Responsable de l’Unité : Xavier Houard
Nom du Responsable de l’Équipe : Harry Sokol
Adresse : Centre de Recherche Saint-Antoine, Faculté de Médecine, 27 rue de Chaligny, 75012 Paris
Responsable de l’encadrement :
Tél : 06 98 33 33 24 E-mail: camille.danne@inserm.fr
Résumé du projet
Inflammatory Bowel Disease (IBD) are chronic inflammatory conditions of the gastrointestinal tract with increasing prevalence. Current therapies are only partially efficient and associated with potentially severe side effects. New therapeutic strategies with innovative targets are thus urgently needed.
Neutrophils are key players of innate immunity in IBD, but their roles in disease development are neglected compared to those of other immune cells. Essential to host defense, their overactivation can cause chronic inflammation and tissue damage. Converging evidence has highlighted interactions between neutrophils, gut inflammation and microbiota. Notably, numerous IBD susceptibility genes are involved in neutrophil functions related to defense against microbes; and IBD is associated with alterations of the intestinal microbiota. However, the influence of microbiota on neutrophil functions, and the consequences in terms of disease development remain largely unknown.
Microbiota metabolites, including short-chain fatty acids, bile acids, and tryptophan (Trp)-derived metabolites, have shown regulatory effects on immune cell types, such as T cells and macrophages. However, their impact on neutrophils is underexplored.
Based on preliminary data, our objectives are to (i) further explore the influence of two microbiota-derived metabolites (named metab1 and metab2 for confidentiality reasons) on neutrophil functions in homeostasis, and (ii) decipher the effect of these microbiota metabolites on neutrophils in the context of intestinal inflammation. Our project follows systematic approaches and takes advantage of up-to-date technologies (flow cytometry,
scRNAseq and/or proteomics) and access to unique mouse and human samples (bone marrow and intestinal tissue from the murine model of DSS (dextran sodium sulfate)-induced colitis; blood and intestinal tissue from IBD patients of the Saint-Antoine Hospital).
Based on both basic and translational research, this project aims at better understanding the roles played by neutrophils in host-microbiota interactions in homeostasis and intestinal inflammation, and to identify new therapeutic targets for IBD.
Dernières Publications en lien avec le projet :
Danne C, Skerniskyte J, Marteyn B, et al. Neutrophils: from IBD to the gut microbiota. Nat Rev Gastroenterol Hepatol 2024;21:184–197.
Danne C, Michaudel C, Skerniskyte J, et al. CARD9 in neutrophils protects from colitis and controls mitochondrial metabolism and cell survival. Gut 2022:gutjnl-2022-326917
Ce projet s’inscrit-il dans la perspective d’une thèse : A discuter
Ce projet s’inscrit-il dans la perspective d’une thèse : ED394 – Physiology, Pathophysiology and Therapeutics (P2T)