Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Acta Derm Venereol. 2018 Jun 8;98(6):585-593. doi: 10.2340/00015555-2926.
Epigenetics plays an important role in the development and progression of many diseases. There is increasing evidence for the importance of epigenetic modifications in the progression of psoriasis. The aim of this study was to examine the role and potential mechanism of action of 5-hydroxymethylcytosine (5-hmC) and ten-eleven translocation-2 (TET2) in psoriasiform dermatitis in mice. Immunohistochemical staining was performed on psoriasis patients and healthy controls. Topical application of imiquimod cream to the dorsal skin of mice was used to induce psoriasiform dermatitis. In comparison with healthy controls, 5-hmC was more extensive and intense in the skin lesions from psoriasis patients. TET2 and 5-hmC were highly expressed in imiquimod-induced psoriasiform skin lesions. Importantly, knockdown of TET2 expression in mice attenuated the psoriasiform phenotype and the expression levels of proinflammatory cytokines (interleukin-17A and -17F and interferon-?) and the chemokine CXCL1 in the lesional skin of mice. This is the first demonstration of a critical role for TET2 in psoriasiform dermatitis in a mouse model, and indicates that 5-hmC may serve as a potential biomarker of psoriasis.
表观遗传学在许多疾病的发展和进展中起着重要作用。越来越多的证据表明，表观遗传修饰在银屑病的进展中具有重要意义。本研究旨在探讨 5-羟甲基胞嘧啶（5-hmC）和 ten-eleven 易位酶-2（TET2）在小鼠银屑病样皮炎中的作用及其潜在作用机制。对银屑病患者和健康对照者进行免疫组织化学染色。采用咪喹莫特乳膏涂敷于小鼠背部皮肤诱导银屑病样皮炎。与健康对照组相比，银屑病患者皮损中 5-hmC 更为广泛和强烈。TET2 和 5-hmC 在咪喹莫特诱导的银屑病样皮肤病变中高表达。重要的是，在小鼠中敲低 TET2 的表达可减轻银屑病样表型以及皮损中促炎细胞因子（白细胞介素-17A 和 -17F 以及干扰素-γ）和趋化因子 CXCL1 的表达水平。这是首次在小鼠模型中证明 TET2 在银屑病样皮炎中的关键作用，并表明 5-hmC 可能作为银屑病的潜在生物标志物。
