功能乳酸菌通过RegIIIγ/MyD88介导的肠道黏膜免疫作用及其分子调节机制研究

Probiotics Lactobacillus is known to modulate intestinal microbiota, ,relieving allergies and inhibiting intestinal inflammation both in human and laboratory animals. Our preliminary study shown that Lactobacillus regulated mucosal immune balance in intestine and maintain the stability of the intestinal function through RegIIIγ/MyD88 pathway, but immunological mechanism is still not clear. In out study, we will use two genetic mouse models including RegⅢγ-/- knockout and ΔT/LTi cell-specific MyD88 knockout mouse models, 1) to determine whether the regulation of Lactobacillus for intestinal flora is mediated by RegIIIγ/MyD88; 2) to determine the regulation of Lactobacillus on MyD88 and IL-1R-MyD88 pathway mediated by microorganisms via Csf2; 3) to determine the effect of Lactobacillus on Treg cells generating. 4) to determine the role of Lactobacillus on regulate signal transduction and the body's immune balance between intestinal microbial and monocyte macrophages in Enteritis through RegIIIγ/MyD88 signaling. Completion of this project will provide rich information on the mechanisms that Lactobacillus regulated intestinal mucosal immune and maintenance of intestinal stability is mediated by RegIIIγ/MyD88. A better understanding of Lactobacillus should provide new insights into meceanisms for poteneial therapeutic.

乳酸菌作为益生菌是人和动物肠道中的重要常在菌，在维持肠道的微生态平衡、缓解过敏、抑制肠道炎症反应等方面有重要作用。本课题组前期研究发现功能乳酸菌通过RegIIIγ/MyD88分子信号途径调节肠道黏膜免疫平衡而发挥维持宿主肠道功能稳定，但其具体影响肠道哪些微生物变化及肠道免疫细胞功能等机制尚不明确。本项目拟用RegⅢγ-/-鼠和ΔT/Lti细胞MyD88 特异性敲除鼠，检测肠道RegIIIγ/MyD88介导乳酸菌对肠道菌群影响；乳酸菌调节MyD88及IL-1R–MyD88途径介导对Csf2调控作用；对Treg细胞生成影响；在肠道炎症条件下如何调控微生物与肠道单核细胞之间的分子信息传递及对肠道免疫功能的影响。本研究将阐明乳酸菌通过RegIIIγ/MyD88调节肠道黏膜免疫功能、维持肠道微环境稳定的分子机制，研究结果将为乳酸菌免疫调节机制的全面揭示和应用乳酸菌生物制剂防治疾病奠定理论基础。

乳酸菌作为益生菌是人和动物肠道中的重要常在菌，在维持肠道的微生态平衡、缓解过敏、抑制肠道炎症反应等方面有重要作用。肠道上皮是机体内最大的黏膜屏障，其产生的抑菌因子胰岛再生源蛋白IIIγ（RegIIIγ）是肠道先天黏膜免疫中的重要成分。本课题组前期研究发现功能乳酸菌通过RegIIIγ/MyD88分子信号途径调节肠道黏膜免疫平衡而发挥维持宿主肠道功能稳定，但其具体影响肠道哪些微生物变化及肠道免疫细胞功能等机制尚不明确。本项目使用RegIIIγ肠道特异性基因敲除鼠进行的主要研究内容：1．研究RegIIIγ介导乳酸菌对肠道菌群结构的影响。2. 研究在DSS诱导小鼠急性肠道炎症情况下，乳酸菌通过RegIIIγ/MyD88信号通路调控肠道免疫系统动态平衡。本研究阐明乳酸菌通过RegIIIγ调节肠道上皮黏膜菌群结构和免疫功能、维持肠道微环境稳定的分子机制，研究结果将为乳酸菌免疫调节机制的全面揭示和应用乳酸菌生物制剂防治疾病奠定理论基础。