RIG‐I antiviral signaling drives interleukin‐23 production and psoriasis‐like skin disease

نویسندگان

  • Huiyuan Zhu
  • Fangzhou Lou
  • Qianqian Yin
  • Yuanyuan Gao
  • Yang Sun
  • Jing Bai
  • Zhenyao Xu
  • Zhaoyuan Liu
  • Wei Cai
  • Fang Ke
  • Lingyun Zhang
  • Hong Zhou
  • Hong Wang
  • Gang Wang
  • Xiang Chen
  • Hongxin Zhang
  • Zhugang Wang
  • Florent Ginhoux
  • Chuanjian Lu
  • Bing Su
  • Honglin Wang
چکیده

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.

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عنوان ژورنال:

دوره 9  شماره 

صفحات  -

تاریخ انتشار 2017