实验性自身免疫性脑脊髓炎
银屑病
生物
信号转导
白细胞介素23
功能(生物学)
细胞生物学
多发性硬化
白细胞介素17
癌症研究
免疫学
免疫系统
作者
Ruirui He,Songfang Wu,Ru Gao,Jianwen Chen,Qianwen Peng,Huijun Hu,Liwen Zhu,Yanqin Du,Wanwei Sun,Xiaojian Ma,Huazhi Zhang,Zhenzhong Cui,Heping Wang,Bradley N. Martin,Yueying Wang,Cunjin Zhang,Chenhui Wang
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2021-05-15
卷期号:206 (10): 2353-2365
被引量:17
标识
DOI:10.4049/jimmunol.2001223
摘要
Abstract IL-17A plays an essential role in the pathogenesis of many autoimmune diseases, including psoriasis and multiple sclerosis. Act1 is a critical adaptor in the IL-17A signaling pathway. In this study, we report that an anti-sense long noncoding RNA, TRAF3IP2-AS1, regulates Act1 expression and IL-17A signaling by recruiting SRSF10, which downregulates the expression of IRF1, a transcriptional factor of Act1. Interestingly, we found that a psoriasis-susceptible variant of TRAF3IP2-AS1 A4165G (rs13210247) is a gain-of-function mutant. Furthermore, we identified a mouse gene E130307A14-Rik that is homologous to TRAF3IP2-AS1 and has a similar ability to regulate Act1 expression and IL-17A signaling. Importantly, treatment with lentiviruses expressing E130307A14-Rik or SRSF10 yielded therapeutic effects in mouse models of psoriasis and experimental autoimmune encephalomyelitis. These findings suggest that TRAF3IP2-AS1 and/or SRSF10 may represent attractive therapeutic targets in the treatment of IL-17–related autoimmune diseases, such as psoriasis and multiple sclerosis.
科研通智能强力驱动
Strongly Powered by AbleSci AI