Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity.

ABSTRACT: Innate lymphoid cells (ILCs) and CD4⁺ T cells produce IL-22, which is critical for intestinal immunity. The microbiota is central to IL-22 production in the intestines; however, the factors that regulate IL-22 production by CD4⁺ T cells and ILCs are not clear. Here, we show that microbiota-derived short-chain fatty acids (SCFAs) promote IL-22 production by CD4⁺ T cells and ILCs through G-protein receptor 41 (GPR41) and inhibiting histone deacetylase (HDAC). SCFAs upregulate IL-22 production by promoting aryl hydrocarbon receptor (AhR) and hypoxia-inducible factor 1α (HIF1α) expression, which are differentially regulated by mTOR and Stat3. HIF1α binds directly to the Il22 promoter, and SCFAs increase HIF1α binding to the Il22 promoter through histone modific

SUBMITTER: Yang W 

PROVIDER: S-EPMC7478978 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature