克罗恩病（CD）是一种预后差、致残率高的免疫相关性肠道炎症性疾病。课题组首次发现肠罗斯氏菌（R.intestinalis）鞭毛蛋白在CD中通过肠上皮细胞TLR5发挥抑炎作用，下调吲哚胺2,3-双加氧酶-1（IDO1）的表达，促进NCR+ILC3的活化及分泌。据此推测：R.intestinalis鞭毛蛋白在CD中通过TLR5调控IDO1介导肠道色氨酸代谢并活化NCR+ILC3而抑制炎症。课题组将采用基因工程鼠及药物干预鼠，阐明TLR5调控IDO1是鞭毛蛋白介导色氨酸代谢的关键通路，色氨酸代谢产物吲哚-3-甲醛是鞭毛蛋白调控NCR+ILC3活化的关键物质，ILC3是鞭毛蛋白抑炎过程中调控的关键效应细胞，并在临床及细胞水平验证。同时阐明TLR5调控IDO1的分子机制。揭示R.intestinalis鞭毛蛋白在CD中调控免疫代谢的机制，为该病诊治提供新策略，有望发现有自主知识产权的全新潜在靶向药物

Crohn’s disease (CD) is a chronic recurrent autoimmune disease with poor prognosis and high morbidity. We discovered that R.intestinalis flagellin plays a significant anti-inflammatory role in CD through Toll-like receptor 5(TLR5) of intestinal epithelial cells, which down-regulates the expression of indoleamine 2,3-dioxygenase-1 (IDO1) and promotes the activation and secretion of NCR+ type 3 innate lymphoid cell (ILC3). Thus, we hypothesize that R.intestinalis flagellin exerts anti-inflammatory effects through activating NCR+ILC3 by tryptophan metabolism via TLR5 regulating IDO1. We propose to use genetically engineered mice and pharmaceutical intervened mice as well as cell models and clinical data to elucidate that 1) the regulation of IDO1 by TLR5 plays the central role in tryptophan metabolism and inflammation suppression mediated by flagellin, 2) indole-3-aldehyde, a tryptophan metabolite, is critical for flagellin to activate NCR+ILC3, 3) ILC3 is the key effector cell activated by flagellin stimulation in the process of inflammation inhibition. In addition, we will clarify the molecular mechanism by which TLR5 regulates IDO1. This study will reveal the mechanism of R.intestinalis flagellin regulating immunometabolism in CD, and provide new theory for the diagnosis and treatment of CD, which may offer novel potential therapeutic target with independent intellectual property rights.