肠道炎症组织微环境调控3型天然淋巴细胞发育和功能的分子机制研究

肠道炎症性疾病是危害国民健康的一类重大疾病。3型天然淋巴细胞（ILC3）在肠道免疫中有免疫防御和免疫调节功能，有望成为肠道炎症性疾病诊疗的新靶点。炎症环境下肠上皮细胞、其他类型免疫细胞及肠道菌群所发生的病理性改变可通过多种机制调节ILC3，并决定肠道炎症疾病的发生与进程。我们早期的研究显示缺乏ILC3的Ahr缺陷小鼠的肠道上皮细胞分泌IL-7减少、致炎性T细胞应答增强，并存在肠道菌群的失平衡。这些组织微环境的特征性改变可能是Ahr敲除小鼠中ILC3发育和功能障碍的重要影响因素。然而炎症组织微环境的各要素通过何种分子机制如何调控ILC3仍不清楚。本项目将以肠道炎症性疾病模型和基因工程小鼠为工具，利用细胞、分子生物学及生物信息学等手段，研究肠道炎症状态下肠上皮细胞、T细胞以及肠道菌群调控ILC3的分子机制，旨在阐明炎症组织微环境调控ILC3的分子规律，为肠道炎症性疾病的诊疗提供新靶点和新策略。

Intestinal inflammatory diseases are big threats to human health. Group 3 innate lymphoid cells (ILC3) exhibit immune defensive and immune regulatory functions in the intestine. Therefore, ILC3 is considered to be a promising target for the prevention and treatment of intestinal inflammatory diseases. Under inflammatory conditions, pathological changes in intestinal epithelial cells, other types of immune cells as well as intestinal microbiota will influence the development and function of ILC3s. The molecular regulation of ILC3 by the inflammatory microenvironment may determine the progress of intestinal inflammation. Our previous study have shown ILC3 development was impaired in Ahr(Aryl hydrocarbon receptor) knockout mouse. The defective of ILC3 development and function in Ahr knockout mouse was accompanies by a serious of abnormalities in the intestinal microenvironment including decreased level of IL-7 secreted by intestinal epithelial cells, enhanced autoimmune T cell responses and aberrant microflora distribution. These events may fundamentally contribute to the defect of ILC3 in Ahr knockout mouse. However, the molecular mechanism underlying how microenvironmental factors affect the development and functions of ILC3s remain elusive. In this proposal, by utilizing intestinal inflammation animal model, genetically engineered mice, cellular/ molecular techniques and bioinformatic tools, we will determine the molecular regulation of ILC3 development and function by microenvironmental factors in the intestine during inflammation. Our research will elaborate the molecular regulation of ILC3 under inflammatory conditions by the intestinal microenvironment and provide novel insights into the prevention and treatment of intestinal inflammatory diseases.