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

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 and Yingzi Cong ()
Additional contact information
Wenjing Yang: The University of Texas Medical Branch
Tianming Yu: The University of Texas Medical Branch
Xiangsheng Huang: The University of Texas Medical Branch
Anthony J. Bilotta: The University of Texas Medical Branch
Leiqi Xu: The University of Texas Medical Branch
Yao Lu: The University of Texas Medical Branch
Jiaren Sun: The University of Texas Medical Branch
Fan Pan: Johns Hopkins University School of Medicine
Jia Zhou: The University of Texas Medical Branch
Wenbo Zhang: The University of Texas Medical Branch
Suxia Yao: The University of Texas Medical Branch
Craig L. Maynard: University of Alabama at Birmingham
Nagendra Singh: Augusta University
Sara M. Dann: The University of Texas Medical Branch
Zhanju Liu: The Shanghai Tenth People’s Hospital
Yingzi Cong: The University of Texas Medical Branch

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: 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 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-18262-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18262-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-18262-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().