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肠道牛磺酸通过降解多余的线粒体RNA,作为炎症性肠病的一种新型免疫代谢调节剂。

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

作者信息

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

机构信息

Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China.

Center for Neuroimmunology and Health Longevity, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

出版信息

Cell Mol Immunol. 2025 Sep 8. doi: 10.1038/s41423-025-01344-0.

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.

摘要

用于治疗炎症性肠病(IBD)的抗肿瘤坏死因子(TNF)疗法受到无反应和耐药问题的阻碍,凸显了对替代或补充治疗的迫切需求。我们的研究表明,IBD患者肠道组织中牛磺酸显著上调,且与疾病严重程度呈负相关。一项关键发现是,TNF直接诱导肠道上皮细胞中牛磺酸的合成,并增加血管生成素的产生,血管生成素是一种可降解线粒体RNA的核酸酶,已知其可放大炎症反应。通过降解线粒体RNA,血管生成素抑制巨噬细胞中的炎症反应,这表明牛磺酸具有强大的免疫调节作用。这一机制意味着牛磺酸可作为抗TNF疗法的辅助药物,提高其疗效,并通过利用机体的固有免疫调节机制,为IBD和其他慢性炎症性疾病的治疗提供一种新策略。

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