NLRP3炎症小体对炎症性肠病免疫机制影响的研究进展

Impact of NLRP3 inflammasome on immune modulation mechanism in inflammatory bowel disease

炎症性肠病的发病与机体自身免疫内环境密切相关,而NLRP3炎症小体参与机体的固有免疫应答和T细胞免疫应答.慢性炎症阶段,典型的NLRP3炎症小体被过度激活,增加IL-1β和IL-18从固有层巨噬细胞和树突状细胞中的释放, IL-1β和IL-18的释放可诱导T细胞向致病性Th1和Th17的表型分化,从而维持炎症反应.急性期IL-1β主要以髓系细胞来源促进肠上皮细胞的愈合和修复,即NLRP3炎症小体对肠上皮细胞具有保护性的功能.而同时, NLRP3炎症小体介导的IL-1β的表达导致Th17/Treg失衡,这也与IBD的发病密切相关.可以说NLRP3作为肠内稳态的分子开关,通过IL-1β使局部免疫细胞向炎症表型转变.

The pathogenesis of inflammatory bowel disease(IBD)is closely related to the internal immune environment.NLRP3 inflammasome participates in the innate immune response and T cell immune response.During chronic inflammation,typical NLRP3 inflammasomes are activated,thus increasing the secretion of IL-1β and IL-18 from lamina propria macrophages and dendritic cells.The release of IL-1β and IL-18 induces T cells to differentiate into pathogenic Th1 and Th17 phenotypes,maintaining the inflammatory response.In the acute inflammation stage,IL-1β mainly promotes the healing and repair of intestinal epithelial cells.Therefore,NLRP3 inflammasome has a protective effect on intestinal epithelial cells.Besides,the expression of IL-1β leads to Th17/Treg imbalance,which is also closely related to the pathogenesis of IBD.Thus,NLRP3 acts as a molecular switch of intestinal homeostasis by shifting local immune cells toward an inflammatory phenotype via IL-1β.