TET2 通过表观遗传调控参与肿瘤进展和内在免疫稳态。据报道，TET2 参与维持上皮屏障稳态和炎症。在银屑病皮损中检测到异常的表皮屏障功能和 TET2 表达。然而，TET2在银屑病中的作用机制尚未阐明。为了明确TET2在维持上皮屏障稳态中的作用以及银屑病表皮屏障功能障碍的确切表观遗传机制。我们分析了人类银屑病皮肤病变和GEO数据库的数据集，并通过免疫组化检测TET2/5-hmC与屏障分子的表达。我们构建了表皮特异性TET2敲除小鼠，通过甲苯胺蓝渗透实验观察TET2缺陷对表皮屏障功能的影响。此外，我们通过免疫荧光分析了 TET2 特异性敲除小鼠和银屑病模型小鼠中表皮屏障分子表达的变化。我们发现 TET2/5-hmC 表达的降低与人类银屑病病变中屏障分子的失调相关。表皮特异性 TET2 敲除小鼠表现出与异常表皮屏障分子相关的透皮失水量增加。此外，我们观察到角质形成细胞中的 TET2 敲低通过丝聚蛋白启动子甲基化减少了丝聚蛋白的表达。异常的表皮 TET2 通过表皮屏障分子（特别是丝聚蛋白）的表观遗传失调影响表皮屏障的完整性。 TET2 表达减少是导致银屑病表皮屏障异常的关键因素。版权所有 © 2024。由 Elsevier B.V. 出版。

TET2 participates in tumor progression and intrinsic immune homeostasis via epigenetic regulation. TET2 has been reported to be involved in maintaining epithelial barrier homeostasis and inflammation. Abnormal epidermal barrier function and TET2 expression have been detected in psoriatic lesions. However, the mechanisms underlying the role of TET2 in psoriasis have not yet been elucidated.To define the role of TET2 in maintaining epithelial barrier homeostasis and the exact epigenetic mechanism in the dysfunction of the epidermal barrier in psoriasis.We analyzed human psoriatic skin lesions and datasets from the GEO database, and detected the expression of TET2/5-hmC together with barrier molecules by immunohistochemistry. We constructed epidermal-specific TET2 knockout mice to observe the effect of TET2 deficiency on epidermal barrier function via toluidine blue penetration assay. Further, we analyzed changes in the expression of epidermal barrier molecules by immunofluorescence in TET2-specific knockout mice and psoriatic model mice.We found that decreased expression of TET2/5-hmC correlated with dysregulated barrier molecules in human psoriatic lesions. Epidermal-specific TET2 knockout mice showed elevated transdermal water loss associated with abnormal epidermal barrier molecules. Furthermore, we observed that TET2 knockdown in keratinocytes reduced filaggrin expression via filaggrin promoter methylation.Aberrant epidermal TET2 affects the integrity of the epidermal barrier through the epigenetic dysregulation of epidermal barrier molecules, particularly filaggrin. Reduced TET2 expression is a critical factor contributing to an abnormal epidermal barrier in psoriasis.Copyright © 2024. Published by Elsevier B.V.