title: RIG-I antiviral signaling drives interleukin-23 production and psoriasis-like skin disease.
abstract: 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-κB) 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.
authors.affiliation: 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.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Fangzhou
authors.initials: F
authors.lastname: Lou
authors.affiliation: 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.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Yin
authors.affiliation: 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.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Bai
authors.affiliation: 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.
authors.forename: Zhenyao
authors.initials: Z
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Zhaoyuan
authors.initials: Z
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
authors.affiliation: 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.
authors.forename: Fang
authors.initials: F
authors.lastname: Ke
authors.affiliation: 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.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Research Centre for Experimental Medicine of Rujin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Research Centre for Experimental Medicine of Rujin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhugang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore City, Singapore.
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.affiliation: 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.
authors.forename: Chuanjian
authors.initials: C
authors.lastname: Lu
authors.affiliation: 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.|Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Su
authors.affiliation: 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 honglin.wang@sjtu.edu.cn.|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.|Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
authors.forename: Honglin
authors.identifier: 0000-0001-6302-6927
authors.initials: H
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D002675:Child, Preschool; D000071457:DEAD Box Protein 58 / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D053759:Interleukin-23 / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D016328:NF-kappa B / Q000276:immunology; D011565:Psoriasis / Q000276:immunology* / Q000473:pathology; D012327:RNA Virus Infections / Q000276:immunology; D012328:RNA Viruses / Q000276:immunology; D011971:Receptors, Immunologic; D015398:Signal Transduction; D012867:Skin / Q000276:immunology / Q000473:pathology; D012871:Skin Diseases / Q000276:immunology* / Q000473:pathology; D055815:Young Adult
chemical_list: D053759:Interleukin-23; D016328:NF-kappa B; D011971:Receptors, Immunologic; C452820:RIGI protein, human; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58
keywords: DCs; NF‐κB; RIG‐I; interleukin‐23; psoriasis