5-HT/5-HTR7信号轴在溃疡性结肠炎中调控调节性B细胞作用机制研究

溃疡性结肠炎（UC）目前病因及发病机制未明，研究认为胃肠神经内分泌肽/胺与免疫细胞相互作用是其重要的致病机制之一。调节性B细胞（Breg）在维持肠道免疫稳态中发挥重要作用。肠道嗜铬细胞（ECs）产生的五羟色胺（5-HT）通过免疫调控影响UC进程，但其免疫调节作用尤其对Breg的影响尚不明确。本课题组前期研究发现活动期UC患者Breg比例及其分泌IL-10降低，5-HT水平与Breg正相关，UC患者中Breg表面5-HT7R表达增加，提示5-HT可能通过调控Breg功能参与UC炎症发生。因此，我们提出假说：5-HT通过5-HTR7调控Breg产生IL-10的能力，从而影响UC肠道炎症的进展。本课题组拟利用UC小鼠模型、患者样本，通过RNA测序、流式细胞分析、WB等方法从细胞、分子和整体不同水平探究UC中5-HT通过其受体下游通路调控Breg及UC进展的分子机制，为UC治疗提供新的理论基础。

The etiology and pathogenesis of ulcerative colitis (UC) is not clear, and accumulating evidence suggests that gastrointestinal neuroendocrine peptide/amine interaction with immune cells is one of the important pathogenic mechanisms. Regulatory B cells (Breg), as immunoregulatory cells, play an important role in maintaining intestinal immune homeostasis. Serotonin (5-hydroxytryptamine, 5-HT) produced by intestinal Enterochromaffin cells (ECs), affects the development and severity of UC through immune regulation, but its immunoregulatory effect, especially the effect of Breg, is poorly understood. The previous study of our group found that the number of Breg and its secretion IL-10 decreased in UC patients at the active stage, while the level of 5-HT was positively correlated with Breg, and the expression of 5-HT7R on Breg increased in UC patients. 5-HT did not change the proportion of Breg, but increased the production of IL-10 by Breg, suggesting that 5-HT may be involved in UC by regulating Breg. Therefore, we proposed a hypothesis: 5-HT regulates Breg's ability to produce IL-10 through 5-HTR7, thus affecting the progression of intestinal inflammation in UC. Based on the previous results, our group intends to apply DSS-induced colitis mouse model and patient samples, with RNA sequencing, flow cytometry, western and other methods, to explore the molecular mechanism of 5-HT in regulating Breg through its receptor to influence the progression of UC, and provide a new theoretical foundation for UC.