核苷酸结合寡聚化结构域样受体含pyrin结构域蛋白6在炎症性肠病中作用机制研究进展

Role of NLRP6 in inflammatory bowel disease

炎症性肠病(inflammatory bowel disease,IBD)是一种病因未明的慢性肠道炎症性疾病,症状易反复发作,迁延不愈,治疗手段及疗效有限.近期有较多研究表明核苷酸结合寡聚化结构域样受体含pyrin结构域蛋白6(NLR family,pyrin domain containing6,Nlrp6)在IBD及相关肿瘤方面具有调节肠道免疫及微生物菌群的重要作用,Nlrp6促进白细胞介素(interleukin,IL)-18及抗菌肽的分泌,IL-18可抑制IL-22BP的产生,增强IL-22作用,并通过MyD88通路来促进上皮细胞增殖;Nlrp6还可通过Toll-like receptors调节杯状细胞分泌Mucoprotein2,清除肠道细菌,调节肠道免疫功能及维持肠道菌群稳态.由于IBD有一定癌变倾向,研究人员发现Nlrp6可作用于NOTCH及Wnt靶点,激活趋化因子配体5及IL-6信号通路,调节上皮细胞增殖,影响IBD相关性结直肠癌.本文就Nlrp6在IBD中的作用机制作一综述.

Inflammatory bowel disease(IBD)is a chronic intestinal inflammatory disease of unknown etiology.The symptoms of IBD are prone to recurrent episodes,and there is currently limited treatment and efficacy.Recently,there have been many studies showing that the nucleotide-binding oligomerization domain-like receptor containing the pyrin domain containing protein(NLR family,pyrin domain containing 6,NLRP6)regulates intestinal immunity and microorganisms in inflammatory bowel disease and related tumors.NLRP6 promotes the secretion of interleukin(IL)-18 and antimicrobial peptides,and IL-18 can inhibit the production of IL-22BP,enhance the role of IL-22,and promote the proliferation of epithelial cells through the MyD88 pathway.NLRP6 also regulates the secretion of mucoprotein 2 by goblet cells via Toll-like receptors,clears intestinal bacteria,regulates intestinal immune function,and maintains intestinal flora.Because IBD is associated with a tendency of malignant transformation,and researchers have found that NLRP6 can act on NOTCH and Wnt,activate chemokine ligand 5 and IL-6 signaling,regulate epithelial cell proliferation,and affect the development of IBDrelated colorectal cancer.This article reviews the role of NLRP6 in IBD.