Song Cuihao, Sun Jie, Zhao Zhenkai, Zhang Xu, Ding Xiangyu, Liang Xiaoqiang, Bai Jia, Xing Liyuan, Gong Lingling, Li Chengxin, Lin Biwen
Department of Dermatology, PLA General Hospital, Beijing, China.
305 Hospital of People's Liberation Army, Beijing, China.
Balkan Med J. 2024 May 3;41(3):174-185. doi: 10.4274/balkanmedj.galenos.2024.2024-1-96.
Psoriasis is a chronic inflammatory skin disease that has no cure. While the specific cause of psoriasis is unknown, interactions between immune cells and inflammatory cytokines are believed to be important in its pathogenesis. Thymic stromal lymphopoietin (TSLP) is a cytokine produced by epithelial cells that profoundly affects dendritic cells (DCs) and is involved in allergy and inflammatory diseases. In some studies, its expression is higher in the skin of psoriasis patients, whereas it is increased in treated psoriasis patients when compared with untreated patients in others.
To investigate the role of TSLP in the pathogenesis of psoriasis.
In vitro and in vivo study.
To investigate the effect of TSLP on psoriasis in vivo, a mouse psoriasis model and shRNA targeting TSLP to reduce its expression were used. Mouse primary bone marrow dendritic cells (BMDCs) were cultured in vitro and used to investigate the signaling pathways activated by TSLP. Results: We found that reducing TSLP expression in psoriasis skin alleviated disease severity. TSLP activated the Janus kinase (JAK)/SYK pathway in psoriatic skin. In vitro studies with BMDCs demonstrated that TSLP increased DC maturation through the JAK/SYK pathway and activated DCs-secreted cytokines that stimulated CD4 T cells to develop into T helper 17 (Th17) cells by activating STAT3 signaling. The JAK/SYK pathway inhibitor reduced the effect of TSLP on activating BMDCs and promoting Th17 differentiation by CD4 T cells.
These findings indicated that TSLP exerted its immune-modulating effect in psoriasis through the JAK/SYK pathway.
银屑病是一种无法治愈的慢性炎症性皮肤病。虽然银屑病的确切病因尚不清楚，但免疫细胞与炎症细胞因子之间的相互作用被认为在其发病机制中起重要作用。胸腺基质淋巴细胞生成素（TSLP）是一种由上皮细胞产生的细胞因子，它对树突状细胞（DCs）有深远影响，并参与过敏和炎症性疾病。在一些研究中，银屑病患者皮肤中TSLP的表达较高，而在另一些研究中，与未治疗的患者相比，接受治疗的银屑病患者中TSLP的表达有所增加。
研究TSLP在银屑病发病机制中的作用。
体外和体内研究。
为了研究TSLP在体内对银屑病的影响，使用了小鼠银屑病模型和靶向TSLP以降低其表达的短发夹RNA（shRNA）。体外培养小鼠原代骨髓树突状细胞（BMDCs），用于研究TSLP激活的信号通路。结果：我们发现降低银屑病皮肤中TSLP的表达可减轻疾病严重程度。TSLP激活了银屑病皮肤中的Janus激酶（JAK）/脾酪氨酸激酶（SYK）通路。对BMDCs的体外研究表明，TSLP通过JAK/SYK通路增加DC成熟，并激活DC分泌的细胞因子，这些细胞因子通过激活信号转导和转录激活因子3（STAT3）信号刺激CD4 T细胞发育为辅助性T细胞17（Th17）细胞。JAK/SYK通路抑制剂降低了TSLP对激活BMDCs和促进CD4 T细胞Th17分化的作用。
这些发现表明，TSLP通过JAK/SYK通路在银屑病中发挥免疫调节作用。
