Zhang Yuxi, Xu Xiaoqing, Zhang Xiaojing, Ni Shuangying, Chen Donger, Cheng Yuqi, Liu Xiaonan, Cui Niannian, Tang Lili, Cheng Hui, Zhou Fusheng
Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China.
Institute of Dermatology, Anhui Medical University, Hefei, Anhui, China.
Exp Dermatol. 2025 Apr;34(4):e70079. doi: 10.1111/exd.70079.
Psoriasis is a chronic inflammatory skin disease. The excessive activation of proinflammatory cytokines interleukin-17 (IL-17), IL-23 and T helper cell 17(Th17) is the main pathogenic factor. In addition, the dysfunction of suppressor cells such as regulatory T cells (Tregs) and the imbalance of the Th17/Treg ratio also play important roles in the pathogenesis of psoriasis. By testing the immune function of peripheral Tregs in psoriasis, psoriasis treated with anti-IL-17 biologics, and healthy controls, we found that the number and function of psoriatic peripheral Tregs were abnormal, and Tregs differentiated from 'inhibitory' to 'inflammatory' cells in the inflammatory environment, which may be the cause of Tregs dysfunction in psoriasis. We also found through the assay for targeting accessible chromatin with high-throughput sequencing (ATAC-seq) analysis that the chromatin accessibility of psoriatic peripheral Tregs was significantly higher than that of healthy controls and decreased after treatment, which may be related to INO80, a gene that controls changes in chromatin tightness or relaxation status. In addition, the differentially expressed genes (DEGs) of three groups, such as NCAM2, CDH18, ZEB1 and CCDC22, were mainly concentrated in the signalling pathways related to effector T(Teff) cell aggregation and Tregs dysfunction. This study provides an important basis for the study of peripheral Tregs dysfunction in psoriasis.
银屑病是一种慢性炎症性皮肤病。促炎细胞因子白细胞介素-17（IL-17）、IL-23和辅助性T细胞17（Th17）的过度激活是主要致病因素。此外，调节性T细胞（Tregs）等抑制性细胞功能障碍以及Th17/Treg比例失衡在银屑病发病机制中也起重要作用。通过检测银屑病患者、接受抗IL-17生物制剂治疗的银屑病患者以及健康对照者外周血Tregs的免疫功能，我们发现银屑病患者外周血Tregs的数量和功能异常，且在炎症环境中Tregs从“抑制性”细胞分化为“炎性”细胞，这可能是银屑病中Tregs功能障碍的原因。我们还通过靶向可及染色质高通量测序（ATAC-seq）分析检测发现，银屑病患者外周血Tregs的染色质可及性显著高于健康对照者，治疗后降低，这可能与控制染色质紧密或松弛状态变化的INO80基因有关。此外，三组的差异表达基因（DEGs），如NCAM2、CDH18、ZEB1和CCDC22，主要集中在与效应T（Teff）细胞聚集和Tregs功能障碍相关的信号通路中。本研究为银屑病外周血Tregs功能障碍的研究提供了重要依据。
