TY - JOUR
T1 - High salt promotes autoimmunity by TET2-induced DNA demethylation and driving the differentiation of Tfh cells
AU - Wu, Haijing
AU - Huang, Xin
AU - Qiu, Hong
AU - Zhao, Ming
AU - Liao, Wei
AU - Yuan, Shuguang
AU - Xie, Yubing
AU - Dai, Yong
AU - Chang, Christopher
AU - Yoshimura, Akihiko
AU - Lu, Qianjin
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China (No. 81210308042, No. 81430074, No. 81220108017 and No. 30972745), the programs of Science-Technology Commission of Hunan province (2011FJ2007, 2011TP4019-7, 2012WK3046 and 2012TT2015), the Fundamental Research Funds for the Central Universities and the National Key Clinical Specialty Construction Project of National health and Family Planning Commission of the People's Republic of China.
PY - 2016/6/21
Y1 - 2016/6/21
N2 - 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.
AB - 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.
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U2 - 10.1038/srep28065
DO - 10.1038/srep28065
M3 - Article
C2 - 27325182
AN - SCOPUS:84976274975
SN - 2045-2322
VL - 6
JO - Scientific Reports
JF - Scientific Reports
M1 - 28065
ER -