Nutrients modulate T cell differentiation and function. (A) Glucose metabolism (via glycolysis) promotes the differentiation of the indicated CD4⁺ T cell subsets and the generation of CD4⁺ and CD8⁺ effector T cells (Teff) and Tem CD8⁺ T cells. Glycolysis limits FOXP3 expression or stability but is upregulated in activated, proliferating Treg cells. (B) The contributions of intracellular amino acids (glutamine, leucine, isoleucine, arginine, serine, and methionine) to CD4⁺ T cell differentiation and Teff and memory (Tmem) CD8⁺ T cell responses are indicated. (C) SCFAs, including acetate, butyrate, and propionate, are derived from the fermentation of dietary fiber by intestinal microbiota. SCFAs alter the differentiation of the indicated CD4⁺ and CD8⁺ T cell subsets, which can occur via signaling through GPCRs or inhibiting HDACs. Diet-derived LCFAs regulate the indicated T cell populations. LCFAs promote Trm cell formation through fatty acid binding proteins (FABPs). Further, dietary TVA and linoleic acid, which are both LCFAs, enhance CD8⁺ T cell function and antitumor immunity. (D) Cholesterol promotes CD8⁺ T cell exhaustion and inhibits Tc9 cell generation in the TME. Intestinal bile acid derivatives (3-oxoLCA, isoalloLCA, and isoDCA) exert differential effects on the generation of Th17 and pTreg cells, as indicated. In particular, bile acid metabolites, including 3-oxoLCA, can promote pTreg cell accumulation in the colon through the vitamin D receptor (VDR). Constitutive androstane receptor (CAR) limits inflammation by detoxifying bile acids and promoting IL-10–producing CD4⁺ T cells in the intestine. Farnesoid X receptor (FXR) in DCs is suppressed by isoDCA, thereby promoting pTreg cell differentiation.