Fiche publication
Date publication
octobre 2025
Journal
Nature metabolism
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DE CARVALHO BITTENCOURT Marcelo
,
Dr D'AVENI-PINEY Maud
Tous les auteurs :
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
Lien Pubmed
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.
Référence
Nat Metab. 2025 10 21;:
