Reg4基因通过调节性B细胞促进炎症性肠病的发生

Reg4 protein, a member of regenerating gene family, which belongs to calcium-dependent lectin gene superfamily, represents a group of small secretory proteins. It is associated with diabetes,chronic inflammation and tumor, especially gastrointestinal tumors. Our previous studies found that Reg4 could regulate the homeostasis of gut microbiota and affect the incidence and development of gut-associated diseases such as colitis and obesity.Reg4 also affect the development of gut immune systerm,especially the accumulation of regulatory B cells in associated gut tissues .So, we hypothesized that Reg4 may be play an important role in the development of chronic gut deseases trough regulatory B cells which be regulated by gut microbiota. The research results will provide a theoretical basis and a new therapeutic target for the clinical treatment of inflammatory bowel disease。

Reg4（regenerating islet-derived family member 4）是Reg基因家族的成员之一，该家族属于钙离子依赖性植物凝集素超家族，由一系列小的分泌性蛋白组成。文献报道Reg基因家族与糖尿病、慢性炎症、肿瘤尤其是消化道肿瘤密切相关。因此我们构建了Reg4基因肠条件过表达鼠，前期研究发现Reg4基因能够调控肠道菌群构成，促进炎症性肠道疾病的发生；同时Reg4能影响肠免疫细胞群的改变，尤其是调节性B细胞在肠免疫器官中的聚集。基于这些事实，我们假定Reg4通过改变肠道菌群进而影响肠免疫系统的形成，通过调节性B细胞在炎症性肠炎发生过程中起着重要的调节作用。研究结果将为临床炎症性肠病的治疗提供新的理论基础和治疗靶点。

本课题通过构建Reg4转基因鼠，对比分析野生鼠与Reg4基因肠条件过表达鼠、Reg4敲除鼠，通过构建DSS急性肠炎模型和高脂饮食诱导的慢性肠炎模型确定Reg4基因在炎症性肠病发生和发展过程中的关键调控作用。并通过流式分析特征了Reg4基因相关的肠免疫细胞群，发现Reg4促进肠不同免疫器官中调节性B细胞的产生和聚集，进一步研究围绕Reg4调控的调节性B细胞在炎症性肠病发生发展过程中的作用机制详细展开，结果发现Reg4通过影响肠道菌群构成促进肠免疫器官中调节性B细胞的产生和聚集，进而增强炎症因子IL-35的表达和分泌，促进肠局部炎症的发生和发展，进而促进炎症性肠病的发展进程。