Abnormal epigenetic modifications in peripheral blood mononuclear cells from patients with alopecia areata

作者：Zhao, M.; Liang, G.; Wu, X.; Wang, S.; Zhang, P.; Su, Y.; Yin, H.; Tan, Y.; Zhang, J.; Lu, Q.^*

来源：British Journal of Dermatology, 2012, 166(2): 266-273.

DOI：10.1111/j.1365-2133.2011.10646.x

• CUTANEOUS LUPUS-ERYTHEMATOSUS
• T-CELLS
• HISTONE MODIFICATIONS
• DNA METHYLATION
• BINDING-PROTEINS
• CD4+T CELLS
• DEMETHYLATION
• ASSOCIATION
• PATTERNS
• PROMOTER

Background Alopecia areata (AA) is a hair loss disease caused by T-cell-mediated autoimmune reactions against anagen-stage hair follicles. Although the exact aetiology is poorly understood, there is evidence to suggest that both genetic and environmental factors are involved in AA pathogenesis.
Objectives To analyse DNA methylation and histone modification patterns in peripheral blood mononuclear cells (PBMCs) of patients with AA.
Methods PBMC samples were obtained from 25 patients with AA and 20 healthy controls. Global DNA methylcytosine levels, as well as histone acetylation and methylation levels, were measured by enzyme-linked immunosorbent assay. mRNA expression levels were determined using real-time quantitative reverse transcription-polymerase chain reaction.
Results Genomic DNA methylation in PBMCs of patients with AA was increased relative to controls. DNMT1, MBD1 and MBD4 expression levels were significantly higher in AA PBMCs than in controls, and DNMT1 transcription levels positively correlated with global DNA methylation levels in patient samples. Histone H3 acetylation was significantly increased and histone H3 lysine 4 methylation was significantly decreased in patient PBMCs compared with healthy controls. Histone H3 acetylation levels were positively correlated with AA disease severity, and with RANTES (CCL5) mRNA expression in PBMCs of patients with AA. These changes were accompanied by increased p300 (EP300), histone deacetylase 1 (HDAC1), myeloid/lymphoid or mixed lineage leukemia (MLL), SET7/9 (SETD7), G9A (EHMT2), JMJD2C (KDM4C) and JARID1A (KDM5A) expression, as well as reduced HDAC2, HDAC7, LSD1 (KDM1A), JMJD2A (KDM4A) and JMJD2B (KDM4B) expression.
Conclusions DNA methylation and histone modification status are altered in PBMCs of patients with AA, possibly due to the deregulation of epigenetic regulatory genes. These changes may contribute to the activation of pathological immune responses in AA.

• 出版日期2012-2
• 单位中南大学