ILC3群细胞与潘氏细胞通过肠道菌群交叉调控在克隆恩病中的研究

IL-22 who mainly originate from ILC3 cells, plays a critical role in the innate immunity by regulating mucosal producing antimicrobial peptides. However, whether IL-22 influence defensins produced by paneth cells in Crohn's disease is unknown. In this proposal, we use paneth-like cell model to elucidate the impact of IL-22 on defensin-production. On the other side, intestinal microbiota is required by the development and IL-22 producing ability of ILC3 cells. NOD2 mutation, decreased defensins expression are closely associated with microbiota dysbiosis in Crohn's disease. Here, we propose a reasonable hypothesis that ILC-3-driven IL-22 production is dependent on the ability of paneth cells to sense microbial signals and impaired NOD2 function leads to decreased IL-22 producing. We use antibiotics-pretreated TNBS mice model and NOD2 deficiency mice to determined whether there exists a microbiota-induced crosstalk between ILC3 cell and paneth cells.

IL-22，主要来源于固有淋巴细胞3群(ILC3)，可通过调节黏膜组织产生抗菌肽在固有免疫中起着重要作用。但IL-22对克隆恩病中潘氏细胞产生防御素HD5、HD6的影响尚不清楚。本课题借助潘氏细胞模型，拟明确IL-22对潘氏细胞产生防御素的影响。另一方面，ILC3群细胞发育及产IL-22的能力依赖于肠道共生菌的存在。而克罗恩病患者NOD2基因的变异，与防御素HD5，HD6分泌减少、肠道菌群失调存在密切联系。因此，我们提出合理假设：ILC3群细胞产IL－22的能力有赖于潘氏细胞感知肠道菌群信号，当NOD2功能缺失无法向ILC3群细胞传递由肠道菌群介导的信号时，IL-22产生减少。本课题拟通过抗生素预处理的TNBS小鼠模型和NOD2缺乏小鼠模型阐明潘氏细胞感知肠道细菌信号的功能缺失是否影响ILC3群细胞产生IL-22的水平，从而建立ILC3群细胞与潘氏细胞通过肠道菌群互相交叉调控的关系。