RIG-I antiviral signaling drives interleukin-23 production and psoriasis-like skin disease.
RIG-I antiviral signaling drives interleukin-23 production and psoriasis-like skin disease.
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RIG-I 抗病毒信号驱动白细胞介素 23 的产生和银屑病样皮肤病
DOI：
10.15252/emmm.201607027
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发表时间：
2017-05
影响因子：
11.1
通讯作者：
Wang H
中科院分区：
文献类型：
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作者：
Zhu H;Lou F;Yin Q;Gao Y;Sun Y;Bai J;Xu Z;Liu Z;Cai W;Ke F;Zhang L;Zhou H;Wang H;Wang G;Chen X;Zhang H;Wang Z;Ginhoux F;Lu C;Su B;Wang H
视黄酸诱导基因I（RIG-I）是RNA病毒的主要传感器之一。编码RIG-I蛋白的DDX 58已被新鉴定为银屑病的易感基因。在这里，我们发现RIG-I被其合成配体5′ ppp-dsRNA激活，直接导致IL-23的产生并引发小鼠银屑病样皮肤病。在无菌小鼠或RIG-I缺陷小鼠中，向耳部重复注射IL-23未能诱导IL-23产生和完整的银屑病样皮肤表型。RIG-I对于咪喹莫特（IMQ）诱导的银屑病样小鼠模型中皮肤炎症的完全发展也至关重要。此外，RIG-I-介导的内源性IL-23产生主要局限于通过核因子-κ B（NF-κB）信号传导的CD 11 c+树突状细胞（DC），并在自动调节反馈回路中刺激RIG-I表达。因此，我们的数据表明，宿主通过先天模式识别受体的抗病毒免疫应答的失调可能触发银屑病病理生理学中的皮肤炎症条件。
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.