Ring1a protects against colitis through regulating mucosal immune system and colonic microbial ecology

文献类型： 外文期刊

第一作者： Wang, Yashu

作者： Wang, Yashu;Li, Qianru;Liu, Pingping;Zheng, Huaixin;Tan, Chen;Zhang, Min;Zhang, Hongxia;Miao, Wenqing;Wang, Yuke;Xuan, Xiaoyan;Wang, Peng;Wang, Yashu;Li, Qianru;Liu, Pingping;Zheng, Huaixin;Tan, Chen;Zhang, Min;Zhang, Hongxia;Miao, Wenqing;Wang, Yuke;Xuan, Xiaoyan;Wang, Peng;Zhang, Jiayu;Chen, Lijuan;Wang, Zhen;Yi, Guoqiang;Wang, Peng;Yi, Guoqiang;Xuan, Xiaoyan

作者机构：

关键词： Ring1a; DSS colitis; mucosal immune system; intestinal microbiota; scRNA-seq

期刊名称：GUT MICROBES （ 影响因子：12.2； 五年影响因子：12.4 ）

ISSN： 1949-0976

年卷期： 2023 年 15 卷 2 期

页码：

收录情况： SCI

摘要： Inflammatory bowel disease (IBD) represents a prominent chronic immune-mediated inflammatory disorder, yet its etiology remains poorly comprehended, encompassing intricate interactions between genetics, immunity, and the gut microbiome. This study uncovers a novel colitis-associated risk gene, namely Ring1a, which regulates the mucosal immune response and intestinal microbiota. Ring1a deficiency exacerbates colitis by impairing the immune system. Concomitantly, Ring1a deficiency led to a Prevotella genus-dominated pathogenic microenvironment, which can be horizontally transmitted to co-housed wild type (WT) mice, consequently intensifying dextran sodium sulfate (DSS)-induced colitis. Furthermore, we identified a potential mechanism linking the altered microbiota in Ring1aKO mice to decreased levels of IgA, and we demonstrated that metronidazole administration could ameliorate colitis progression in Ring1aKO mice, likely by reducing the abundance of the Prevotella genus. We also elucidated the immune landscape of DSS colitis and revealed the disruption of intestinal immune homeostasis associated with Ring1a deficiency. Collectively, these findings highlight Ring1a as a prospective candidate risk gene for colitis and suggest metronidazole as a potential therapeutic option for clinically managing Prevotella genus-dominated colitis. We found that PcG protein Ring1a could be a new risk gene for colitis. Ring1a deficiency causes aggravated colitis by regulating the mucosal immune system and colonic microbial ecology.

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