https://scholars.lib.ntu.edu.tw/handle/123456789/641328
標題: | PD-L1 Enhanced by cis-Urocanic Acid on Langerhans Cells Inhibits Vγ4+ γδT17 Cells in Imiquimod-Induced Skin Inflammation | 作者: | Yeh, Chen-Yun Su, Sheng-Han Tan, Yeh Fong Tsai, Tsen-Fang PI-HUI LIANG Kelel, Musin Weng, Hao-Jui Hsiao, Yu-Ping Lu, Chun-Hao Tsai, Ching-Hui Lee, Chih-Hung Clausen, Björn E Liu, Fu-Tong YUNG-LING LEE |
公開日期: | 八月-2023 | 卷: | 143 | 期: | 8 | 起(迄)頁: | 1449 | 來源出版物: | The Journal of investigative dermatology | 摘要: | Psoriasis is an IL-23/IL-17-mediated inflammatory autoimmune dermatosis, and UVB may contribute to immunosuppression and ameliorate associated symptoms. One of the pathophysiology underlying UVB therapy is the production of cis-urocanic acid (cis-UCA) by keratinocytes. However, the detailed mechanism is yet to be fully understood. In this study, we found FLG expression and serum cis-UCA levels were significantly lower in patients with psoriasis than in healthy controls. We also noted that cis-UCA application inhibited psoriasiform inflammation through the reduction of Vγ4+ γδT17 cells in murine skin and draining lymph nodes. Meanwhile, CCR6 was downregulated on γδT17 cells, which would suppress the inflammatory reaction at a distal skin site. We revealed that the 5-hydroxytryptamine receptor 2A, the known cis-UCA receptor, was highly expressed on Langerhans cells in the skin. cis-UCA also inhibited IL-23 expression and induced PD-L1 on Langerhans cells, leading to the attenuated proliferation and migration of γδT-cells. Compared to the isotype control, α-PD-L1 treatment in vivo could reverse the antipsoriatic effects of cis-UCA. PD-L1 expression on Langerhans cells was sustained through the cis-UCA-induced mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. These findings uncover the cis-UCA-induced PD-L1-mediated immunosuppression on Langerhans cells, which facilitates the resolution of inflammatory dermatoses. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/641328 | ISSN: | 0022202X | DOI: | 10.1016/j.jid.2023.02.018 |
顯示於: | 藥學系 |
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