AUTHORS 

Wenjing Yang, Tianming Yu, Xiangsheng Huang, Anthony J. Bilotta, Leiqi Xu, Yao Lu, Jiaren Sun, Fan Pan, Jia Zhou, Wenbo Zhang, Suxia Yao, Craig L. Maynard, Nagendra Singh, Sara M. Dann, Zhanju Liu & Yingzi Cong

SUMMARY

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 modification. SCFA supplementation enhances IL-22 production, which protects intestines from inflammation. SCFAs promote human CD4+ T cell IL-22 production. These findings establish the roles of SCFAs in inducing IL-22 production in CD4+ T cells and ILCs to maintain intestinal homeostasis.

REFERENCES

Yang, W., Yu, T., Huang, X. et al. Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity. Nat Commun 11, 4457 (2020). https://doi.org/10.1038/s41467-020-18262-6

PRODUCT HIGHLIGHTS

The following Bio X Cell in vivo monoclonal antibodies were featured in the publication:

• InVivoMAb anti-mouse CD3ε (Clone 145-2C11, Bio X Cell Catalog no. BE0001-1)
• InVivoMAb anti-mouse CD28 (Clone 37.51, Bio X Cell Catalog no. BE0015-1)
• InVivoPlus anti-mouse CD4 (Clone GK1.5, Bio X Cell Catalog no. BP0003-1)
• InVivoMAb anti-mouse Thy1.2/CD90.2 (Clone 30-H12, Bio X Cell Catalog no. BE0066)
• InVivoPlus mouse IgG2a isotype control (Clone C1.18.4, Bio X Cell Catalog no. BP0085)