机构:[1]Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China[2]Department of Dermatology, Xijing Hospital, The Fourth Military Medical University, Xi’an, China[3]Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China[4]Research Centre for Experimental Medicine of Rujin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[5]Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore City, Singapore[6]Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, The Second Clinical School of Guangzhou University of Chinese Medicine, Guangzhou, China广东省中医院[7]Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China
Retinoic acid inducible-gene I (RIG-I) functions as one of the major sensors of RNA viruses. DDX58, which encodes the RIG-I protein, has been newly identified as a susceptibility gene in psoriasis. Here, we show that the activation of RIG-I by 5'-ppp-dsRNA, its synthetic ligand, directly causes the production of IL-23 and triggers psoriasis-like skin disease in mice. Repeated injections of IL-23 to the ears failed to induce IL-23 production and a full psoriasis-like skin phenotype, in either germ-free or RIG-I-deficient mice. RIG-I is also critical for a full development of skin inflammation in imiquimod (IMQ)-induced psoriasis-like mouse model. Furthermore, RIG-I-mediated endogenous IL-23 production was mainly confined to the CD11c(+) dendritic cells (DCs) via nuclear factor-kappa B (NF-kappa B) signaling, and stimulated RIG-I expression in an auto-regulatory feedback loop. Thus, our data suggest that the dysregulation in the antiviral immune responses of hosts through the innate pattern recognition receptors may trigger the skin inflammatory conditions in the pathophysiology of psoriasis.
基金:
National Natural Science Foundation
of China (Key Program: 31330026, General Program: 31570922 and Key
Program: 81430033), the Leading Academic Discipline Project of the Shanghai
Municipal Education Commission (16XD1402500), the Key Program of the
Shanghai Municipal Education Commission (15431900800), the National
Program on Key Basic Research Project (973 Program, 2014CB541905), the
National Natural Science Foundation of China (Youth Program: 81502723 and
31500730).
第一作者机构:[1]Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China
通讯作者:
通讯机构:[1]Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China[6]Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, The Second Clinical School of Guangzhou University of Chinese Medicine, Guangzhou, China[7]Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China
推荐引用方式(GB/T 7714):
Zhu Huiyuan,Lou Fangzhou,Yin Qianqian,et al.RIG-I antiviral signaling drives interleukin-23 production and psoriasis-like skin disease[J].EMBO MOLECULAR MEDICINE.2017,9(5):589-604.doi:10.15252/emmm.201607027.
APA:
Zhu, Huiyuan,Lou, Fangzhou,Yin, Qianqian,Gao, Yuanyuan,Sun, Yang...&Wang, Honglin.(2017).RIG-I antiviral signaling drives interleukin-23 production and psoriasis-like skin disease.EMBO MOLECULAR MEDICINE,9,(5)
MLA:
Zhu, Huiyuan,et al."RIG-I antiviral signaling drives interleukin-23 production and psoriasis-like skin disease".EMBO MOLECULAR MEDICINE 9..5(2017):589-604