机构：[1]Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Facultyof Basic Medicine, Shanghai Institute of Immunology, Key Laboratory of CellDifferentiation and Apoptosis of Chinese Ministry of Education, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China[2]Xin Hua Hospitalaffiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092,China[3]Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics,Guangdong Medical University, Dongguan 523808, China[4]Shanghai Skin DiseaseHospital, Tongji University, Shanghai 200443, China[5]Department of CardiovascularMedicine, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan[6]Cardiovascular Division, King’s College London, London WC2R 2LS, UK[7]Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
Dendritic cells (DCs) contribute to psoriasis pathogenesis. In a mouse model of imiquimod-induced psoriasiform skin inflammation, we found that p38 alpha activity in Langerhans cells (LCs), a skin-resident subset of DCs, promoted the generation of T cells that produce IL-17, a proinflammatory cytokine that is implicated in autoimmune disease. Deletion of p38 alpha in LCs, but not in other skin or circulating DC subsets or T cells, decreased T cell-mediated psoriasiform skin inflammation in mice. The activity of p38 alpha in LCs specifically promoted IL-17 production from gamma delta and CD4(+) T cells by increasing the abundance of IL-23 and IL-6, two cytokines that stimulate IL-17 secretion. Inhibition of p38 activity through either pharmacological inhibition or genetic deletion also reduced the severity of established psoriasiform skin inflammation. Together, our findings indicate a critical role for p38 alpha signaling in LCs in promoting inflammatory responses in the skin and suggest that targeting p38 alpha signaling in LCs may offer an effective therapeutic approach to treat psoriasis.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31670897, 81471528, 91642104, 81671399]; Ministry of Science and Technology of China (973 Basic Science Project)National Basic Research Program of China [2014CB541803]; Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning; Shanghai Municipal Commission of Health and Family Planning [20154Y0120, 20164Y0127]; Shanghai Sailing Program [17YF1416600]
第一作者机构：[1]Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Facultyof Basic Medicine, Shanghai Institute of Immunology, Key Laboratory of CellDifferentiation and Apoptosis of Chinese Ministry of Education, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China
通讯作者：
推荐引用方式(GB/T 7714)：
Zheng Tingting,Zhao Weiheng,Li Hongjin,et al.p38 alpha signaling in Langerhans cells promotes the development of IL-17-producing T cells and psoriasiform skin inflammation[J].SCIENCE SIGNALING.2018,11(521):doi:10.1126/scisignal.aao1685.
APA：
Zheng, Tingting,Zhao, Weiheng,Li, Hongjin,Xiao, Shuxiu,Hu, Ran...&Huang, Gonghua.(2018).p38 alpha signaling in Langerhans cells promotes the development of IL-17-producing T cells and psoriasiform skin inflammation.SCIENCE SIGNALING,11,(521)
MLA：
Zheng, Tingting,et al."p38 alpha signaling in Langerhans cells promotes the development of IL-17-producing T cells and psoriasiform skin inflammation".SCIENCE SIGNALING 11..521(2018)
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