2026-01-07 中国科学院(CAS)
<関連情報>
- https://english.cas.cn/newsroom/research_news/life/202601/t20260105_1145172.shtml
- https://www.nature.com/articles/s41590-025-02368-4
IL17REL遺伝子は、腸の炎症を制御するIL-17ファミリーサイトカインのデコイ受容体をコードしている The IL17REL gene encodes a decoy receptor of IL-17 family cytokines to control gut inflammation
Qi Li,Xiaoyu Li,Yunwei Lou,Yingying Xing,Wei Yan,Yuan Chen,Guohong Hu,Xinyang Song,Zhanju Liu,Tao Yang & Youcun Qian
Nature Immunology Published:06 January 2026
DOI:https://doi.org/10.1038/s41590-025-02368-4
Abstract
The IL17REL gene locus has been associated with susceptibility to inflammatory bowel disease (IBD). However, whether it encodes a functional protein and whether its IBD risk variants causally contribute to disease pathogenesis remain unknown. Here, we demonstrated that IL17REL encodes a decoy receptor capable of binding interleukin-17 (IL-17) family cytokines and suppressing intestinal inflammation. By contrast, proteins encoded by IBD-associated IL17REL variants lacked this function. We also showed that TGFβ1 induced IL17REL transcription, and its expression positively correlated with TGFB1 levels in IBD. Mechanistically, the IL-17REL protein competed with IL-17RA for IL-17A binding, an ability that is lost in the mutant form. Knock-in of IL17REL in mice alleviated 2,4,6-trinitrobenzene sulfonic acid-induced colitis, whereas knock-in of an IBD-associated IL17REL mutant did not. In addition, therapeutic administration of IL-17REL protein alleviated colitis symptoms. Together, these findings implicate IL-17REL variants in the pathogenesis of IBD and highlight IL-17REL as a potential therapeutic target.
