PDF(Pubmed)
Abstract：
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.
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.
摘要：
炎症性肠病（IBD）是一种突出的慢性免疫介导的炎症性疾病，然而其病因仍然知之甚少，涵盖了遗传学之间复杂的相互作用，豁免权,和肠道微生物组。这项研究发现了一种新的结肠炎相关风险基因，即Ring1a，调节粘膜免疫反应和肠道微生物群。Ring1a缺乏通过损害免疫系统而加剧结肠炎。同时，Ring1a缺乏导致Prevotella属为主的致病微环境，可以水平传播给共同饲养的野生型（WT）小鼠，因此加剧葡聚糖硫酸钠（DSS）诱导的结肠炎。此外，我们发现了一种潜在的机制，将Ring1aKO小鼠中改变的微生物群与降低的IgA水平联系起来，我们证明了甲硝唑可以改善Ring1aKO小鼠的结肠炎进展，可能是通过减少普雷沃氏菌属的丰度。我们还阐明了DSS结肠炎的免疫景观，并揭示了与Ring1a缺乏相关的肠道免疫稳态的破坏。总的来说，这些发现强调了Ring1a是结肠炎的前瞻性候选风险基因,并提示甲硝唑是临床治疗普雷沃氏菌属为主的结肠炎的潜在治疗选择.
我们发现PcG蛋白Ring1a可能是结肠炎的新风险基因。Ring1a缺乏通过调节粘膜免疫系统和结肠微生物生态导致结肠炎加重。
我们发现PcG蛋白Ring1a可能是结肠炎的新风险基因。Ring1a缺乏通过调节粘膜免疫系统和结肠微生物生态导致结肠炎加重。
