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Microbial metabolite Indole-3-propionic acid drives mitochondrial respiration in CD4+ T cells to confer protection against intestinal inflammation

ABSTRACT: 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 the oxidation of fatty acids and amino acids (FAO and AAO), while inhibiting glycolytic capacity. IPA also impacts CD4+ T cell behavior by inhibiting their differentiation to TH1 and TH17 phenotypes. Mechanistically, the metabolic and immune effects of IPA are mediated by Peroxisome Proliferator-Activated Receptor-beta/delta. 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.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Culture Condition:cd4+ Cell, T Cell

DISEASE(S): Inflammatory Bowel Disease

SUBMITTER: Guillaume CHEVREUX

LAB HEAD: Harry Sokol

PROVIDER: PXD057537 | Pride | 2025-08-28

REPOSITORIES: Pride

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			Action	DRS
	2408003.sne	Other
	2408003_CD3_DIA_1_S4-D3_1_11904.d.zip	Other
	2408003_CD3_DIA_2_S4-D4_1_11905.d.zip	Other
	2408003_CD3_DIA_3_S4-D5_1_11906.d.zip	Other
	2408003_CD3_DIA_4_S4-D6_1_11907.d.zip	Other

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