Ring1a protects against colitis through regulating mucosal immune system and colonic microbial ecology
Yashu Wang,
Qianru Li,
Jiayu Zhang,
Pingping Liu,
Huaixin Zheng,
Lijuan Chen,
Zhen Wang,
Chen Tan,
Min Zhang,
Hongxia Zhang,
Wenqing Miao,
Yuke Wang,
Xiaoyan Xuan,
Guoqiang Yi,
Peng Wang
Affiliations
Yashu Wang
Department of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
Qianru Li
Department of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
Jiayu Zhang
Lab of Pathology, Hebei Medical University, Shijiazhuang, China
Pingping Liu
Department of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
Huaixin Zheng
Department of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
Lijuan Chen
Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Livestock and Poultry Multi-omics of MARA, Kunpeng Institute of Modern Agriculture at Foshan, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China
Zhen Wang
Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Livestock and Poultry Multi-omics of MARA, Kunpeng Institute of Modern Agriculture at Foshan, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China
Chen Tan
Department of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
Min Zhang
Department of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
Hongxia Zhang
Department of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
Wenqing Miao
Department of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
Yuke Wang
Department of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
Xiaoyan Xuan
Department of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
Guoqiang Yi
Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Livestock and Poultry Multi-omics of MARA, Kunpeng Institute of Modern Agriculture at Foshan, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China
Peng Wang
Department of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
ABSTRACTInflammatory 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.
