Hypomethylation of IL10 and IL13 promoters in CD4+ T cells of patients with systemic lupus erythematosus.
Interleukin- (IL-)10 and IL-13 play important roles in Th2 cell differentiation and production of autoantibodies in patients with (SLE). However, the mechanisms leading to IL10 and IL13 overexpression in SLE patients are not well understood. In this study, we confirm that the levels of both IL10 and IL13 mRNA in CD4+ T cells and of serum IL10 and IL13 proteins are increased in SLE patients. We show that the DNA methylation levels within IL10 and IL13 gene regulatory domains are reduced in SLE CD4+ T cells relative to healthy controls and negatively correlate with IL10 and IL13 mRNA expression. Moreover, treating healthy CD4+ T cells with the demethylating agent 5-azacytidine (5-azaC) increased IL10 and IL13 mRNA transcription. Together, our results show that promoter methylation is a determinant of IL10 and IL13 expression in CD4+ T cells, and we propose that DNA hypomethylation leads to IL10 and IL13 overexpression in SLE patients.
Zhao
Ming
M
Department of Dermatology, Epigenetic Research Center, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Tang
Jinling
J
Gao
Fei
F
Wu
Xiaoyan
X
Liang
Yunsheng
Y
Yin
Heng
H
Lu
Qianjin
Q
D000293:Adolescent; D000328:Adult; D001374:Azacitidine / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D016022:Case-Control Studies; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D018793:Interleukin-13 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D008297:Male; D008745:Methylation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics
D004791:Enzyme Inhibitors; C508609:IL10 protein, human; D018793:Interleukin-13; D016753:Interleukin-10; D001374:Azacitidine