DNA demethylation of the perforin promoter in CD4(+) T cells from patients with subacute cutaneous lupus erythematosus.
BACKGROUND
Recent evidence indicates that human lupus is an epigenetic disease characterized by impaired T cell DNA methylation. Perforin, a cytotoxic effector molecule, is overexpressed due to hypomethylation of its promoter regulatory elements in CD4(+) T cells from patients with systemic erythematosus lupus (SLE). However, it is unknown whether aberrant expression and methylation of perforin occur in CD4(+) T cells from patients with subacute cutaneous lupus erythematosus (SCLE).


OBJECTIVE
We aimed to compare the perforin expression level and the methylation status of the perforin promoter region in CD4(+) T cells from SCLE patients and healthy controls.


METHODS
We used real-time RT-PCR to compare the perforin mRNA levels, and Western-blot to compare perforin protein levels in CD4(+) and CD8(+) T cells from SCLE patients and healthy controls. Bisulfite sequencing was used to determine the methylation status of the perforin promoter region.


RESULTS
Perforin is overexpressed in SCLE CD4(+) T cells. Demethylation of the perforin promoter region was seen in CD4(+) T cells from patients with SCLE.


CONCLUSIONS
DNA demethylation at the perforin locus contributes to perforin overexpression in SCLE CD4(+) T cells.
Luo
Yongqi
Y
Department of Dermatology, Epigenetic Research Center, Second Xiangya Hospital, Central South University, Changsha, PR China.
Zhang
Xiujuan
X
Zhao
Ming
M
Lu
Qianjin
Q
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008178:Lupus Erythematosus, Cutaneous / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism
C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D054353:Perforin