Hypomethylation and overexpression of CD70 (TNFSF7) in CD4+ T cells of patients with primary Sjögren's syndrome.
BACKGROUND
Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by lymphocytic infiltration and the production of autoantibodies, leading to the destruction of lacrimal and salivary glands. However, very little is known about the pathogenesis of the disorder. CD70 (TNFSF7), a B cell costimulatory molecule, is overexpressed in CD4(+) T cells from patients with systemic erythematosus lupus (SLE) due to the hypomethylation of its promoter.


OBJECTIVE
In this study we asked whether the epigenetic regulation of CD70 expression is abnormal in pSS.


METHODS
CD70 levels in CD4(+) T cells from pSS patients, tinea pedis and healthy controls were measured by real-time RT-PCR and flow cytometry. Bisulphite sequencing was performed to determine the methylation status of the TNFSF7 promoter region.


RESULTS
CD70 expression was significantly elevated and correlated with a decrease in TNFSF7 promoter methylation in pSS CD4(+) T cells compared to controls.


CONCLUSIONS
Demethylation of the CD70 promoter regulatory elements contributes to CD70 overexpression in pSS CD4(+) T cells, and may contribute to autoreactivity.
Yin
Heng
H
Department of Dermatology, Epigenetic Research Center, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
Zhao
Ming
M
Wu
Xiaoyan
X
Gao
Fei
F
Luo
Yongqi
Y
Ma
Le
L
Liu
Sufang
S
Zhang
Guangsen
G
Chen
Jinwei
J
Li
Fen
F
Zuo
Xiaoxia
X
Lu
Qianjin
Q
D000328:Adult; D053282:CD27 Ligand / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000276:immunology; D014008:Tinea Pedis / Q000235:genetics / Q000276:immunology; D055815:Young Adult
D053282:CD27 Ligand; C505771:CD70 protein, human