| 1 | FXYD3 enhances IL-17A signaling to promote psoriasis by competitively binding TRAF3 in keratinocytes显示文摘Psoriasis is a common chronic inflammatory skin disease characterized by inflammatory cell infiltration and epidermal hyperplasia.However,the regulatory complexity of cytokine and cellular networks still needs to be investigated.Here,we show that the expression of FXYD3,a member of the FXYD domain-containing regulators of Na+/K+ATPases family,is significantly increased in the lesional skin of psoriasis patients and mice with imiquimod(IMQ)-induced psoriasis.IL-17A,a cytokine important for the development of psoriatic lesions,contributes to FXYD3 expression in human primary keratinocytes.FXYD3 deletion in keratinocytes attenuated the psoriasis-like phenotype and inflammation in an IMQ-induced psoriasis model.Importantly,FXYD3 promotes the formation of the IL-17R-ACT1 complex by competing with IL-17R for binding to TRAF3 and then enhances IL-17A signaling in keratinocytes.This promotes the activation of the NF-κB and MAPK signaling pathways and leads to the expression of proinflammatory factors.Our results clarify the mechanism by which FXYD3 serves as a mediator of IL-17A signaling in keratinocytes to form a positive regulatory loop to promote psoriasis exacerbation.Targeting FXYD3 may serve as a potential therapeutic approach in the treatment of psoriasis. | Wenjuan Yang Rukun He Hao Qu Wenwen Lian Yue Xue Tao Wang Wenlong Lin Peishuo Zhu Meng Xia Lihua Lai Qingqing Wang | 2023 | Cellular & Molecular Immunology2023，20，3： | 2 |
| 2 | CD97 negatively regulates the innate immune response against RNA viruses by promoting RNF125-mediated RIG-I degradation显示文摘The G protein-coupled receptor ADGRE5(CD97)binds to various metabolites that play crucial regulatory roles in metabolism.However,its function in the antiviral innate immune response remains to be determined.In this study,we report that CD97 inhibits virus-induced type-I interferon(IFN-I)release and enhances RNA virus replication in cells and mice.CD97 was identified as a new negative regulator of the innate immune receptor RIG-I,and RIG-1 degradation led to the suppression of the IFN-I signaling pathway.Furthermore,overexpression of CD97 promoted the ubiquitination of RIG-I,resulting in its degradation,but did not impact its mRNA expression.Mechanistically,CD97 upregulates RNF125 expression to induce RNF125-mediated RIG-I degradation via K48-linked ubiquitination at Lys181 after RNA virus infection.Most importantly,CD97-deficient mice are more resistant than wild-type mice to RNA virus infection.We also found that sanguinarine-mediated inhibition of CD97 effectively blocks VSV and SARS-CoV-2 replication.These findings elucidate a previously unknown mechanism through which CD97 negatively regulates RIG-I in the antiviral innate immune response and provide a molecular basis for the development of new therapeutic strategies and the design of targeted antiviral agents. | Huasong Chang Peili Hou Xuefeng Wang Aibiao Xiang Hao Wu Wenjing Qi Rukun Yang Xue Wang Xingyu Li Wenqi He Guimin Zhao Weiyang Sun Tiecheng Wang Daniel Chang He Hongmei Wang Yuwei Gao Hongbin He | 2023 | Cellular & Molecular Immunology2023，20，12： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员