Format

Send to

Choose Destination
Sci Rep. 2016 Jun 21;6:28065. doi: 10.1038/srep28065.

High salt promotes autoimmunity by TET2-induced DNA demethylation and driving the differentiation of Tfh cells.

Author information

1
Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
2
Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
3
Changsha Blood Center, Changsha, Hunan, China.
4
Clinical medical research center, the Second Clinical medical college of Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China.
5
Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, USA.
6
Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.

Abstract

Follicular helper T cells (Tfh) have been well documented to play a critical role in autoimmunity, such as systemic lupus erythematosus (SLE), by helping B cells. In this study, high salt (sodium chloride, NaCl), under physiological conditions, was demonstrated to increase the differentiation of Tfh. A high-salt diet markedly increased lupus features in MRL/lpr mice. The mechanism is NaCl-induced DNA demethylation via the recruitment of the hydroxytransferase Ten-Eleven Translocation 2 (TET2). Gene silencing of TET2 obviously diminished NaCl-induced Tfh cell polarization in vitro. In addition, the gene expression of sh2d1a, map3k1, spn and stat5b was enhanced after NaCl treatment, consistent with the findings in lupus CD4(+)T cells. However, only spn was directly regulated by TET2, and spn was not the sole target for NaCl. Our findings not only explain the epigenetic mechanisms of high-salt induced autoimmunity but also provide an attractive molecular target for intervention strategies of patients.

PMID:
27325182
PMCID:
PMC4914849
DOI:
10.1038/srep28065
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center