La plateforme ProtéoSeine a contribué à la publication d’un nouvel article dans Nature metabolism :
Résumé :
The gut microbiota and its metabolites critically regulate immune cell phenotype, function and energy metabolism. We screened a collection of gut microbiota-related metabolites to identify modulators of mitochondrial metabolism in T cells. Here we show that indole-3-propionic acid (IPA) stimulates mitochondrial respiration of CD4+ T cells by increasing fatty acid oxidation (FAO) and amino acid oxidation (AAO), while inhibiting glycolytic capacity. IPA also impacts CD4+ T cell behaviour by inhibiting their differentiation to type 1 and type 17 helper T cell phenotypes. Mechanistically, the metabolic and immune effects of IPA are mediated by peroxisome proliferator-activated receptor-β/δ. The administration of IPA rescues mitochondria respiration in mice with gut bacteria depletion or colitis by enhancing FAO and AAO in colonic CD4+ T cells. Adoptive transfer experiments show that IPA acts on CD4+ T cells to exert its protective effect against inflammation. Collectively, our study reveals that the anti-inflammatory effects of IPA are mediated by metabolic reprogramming of CD4+ T cells toward the enhancement of mitochondrial respiration.
Crédit figure : Li Q, de Oliveira Formiga R, Puchois V, Creusot L, Ahmad AH, Amouyal S, Campos-Ribeiro MA, Zhao Y, Harris DMM, Lasserre F, Ellero-Simatos S, Guillou H, Huang Z, Brot L, Hu Y, Chollet L, Danne C, Scandola C, Ledent T, Chevreux G, Argüello RJ, De Carvalho Bittencourt M, Bettinger J, D’Aveni-Piney M, Moulin D, Schreiber S, Aden K, Rolhion N, Michel ML, Wai T, Sokol H. Microbial metabolite indole-3-propionic acid drives mitochondrial respiration in CD4+ T cells to confer protection against intestinal inflammation. Nat Metab. 2025 Oct 21. doi: 10.1038/s42255-025-01396-6. Epub ahead of print. PMID: 41120706.