Commensal microbiota shapes the intestinal immune system by regulating T helper (TH) cell lineage differentiation. For example, Bacteroides fragilis colonization not only optimizes the systemic TH1/TH2 balance, but also can induce regulatory T (Treg) cell differentiation in the gut. In addition, segmented filamentous bacteria (SFB) facilitate the development of TH17 cells in the small intestine. The 17 strains within clusters IV, XIVa, and XVIII of Clostridiales found in human feces can also induce the differentiation and expansion of Treg cells in the colon. Thus, the regulation of TH cell differentiation by commensal bacteria is evident; however, the molecular mechanisms underlying these processes remain uncertain. Recent studies have demonstrated that bacterial components, as well as their metabolites, play a central role in regulating TH cell development. Furthermore, these metabolites can elicit changes in histone posttranslational modification to modify the expression of critical regulators of T cell fate. In this review, we discuss the mechanisms and biological significance of microbiota-dependent TH differentiation.
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