Intestinal taurine acts as a novel immunometabolic modulator of IBD by degrading redundant mitochondrial RNA

肠道牛磺酸通过降解冗余的线粒体RNA,发挥炎症性肠病(IBD)的新型免疫代谢调节作用。

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作者:Le-Xi Wu # ,Jia-Huan Xie # ,Jie-Yu Li # ,Wen-Ping Li ,Xin-Tao Mao ,Ling-Jie Huang ,Hao-Tian Chen ,Jiang-Yan Zhong ,Li-Min Lin ,Shicheng Su ,Yi-Yuan Li ,Qian Cao ,Jin Jin

Abstract

Anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD) is hampered by issues of nonresponse and resistance, highlighting the urgent need for alternative or complementary treatments. Our study revealed significant upregulation of taurine in the intestinal tissues of IBD patients, which was inversely related to the severity of the disease. A key discovery was that TNF directly induced taurine synthesis in intestinal epithelial cells and increased the production of angiogenin, a nuclease that degrades mitochondrial RNA, which is known to amplify inflammatory responses. By degrading mitochondrial RNA, angiogenin inhibits the inflammatory response in macrophages, suggesting a potent immune-modulatory role for taurine. This mechanism implies that taurine could serve as an adjunct to anti-TNF therapies, enhancing their efficacy and providing a novel strategy for the management of IBD and other chronic inflammatory diseases by harnessing the body's innate immune regulatory mechanisms.

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