转录因子ThPok调控NKT细胞在自身免疫性肝炎中的作用探讨

项目名称： 转录因子ThPok调控NKT细胞在自身免疫性肝炎中的作用探讨

项目编号： No.81500434

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 刘夏

作者单位： 浙江大学

项目金额： 18万元

中文摘要： 自身免疫性肝炎（AIH）是一类病因不明的炎症性肝病，而iNKT细胞是一类通过分泌细胞因子促进AIH疾病发展的重要免疫细胞，因此，调控iNKT细胞功能对于控制自身免疫性肝炎具有重要意义。转录因子ThPok能够调控CD4+T细胞的定向分化，但其对于iNKT细胞的调控作用尚不完全清楚。作者之前的研究发现转录因子ThPok能够调控小鼠iNKT细胞的分化发育，并且通过调控iNKT细胞的功能从而促进小鼠自身免疫性肝炎的发生和发展。本课题拟重点研究转录因子ThPok对AIH患者iNKT细胞的调控作用。通过分析AIH患者ThPok表达情况与肝损伤程度的相关性，深入探讨ThPok调控人iNKT细胞的具体机制；探讨抑制iNKT细胞中ThPok表达能否抑制iNKT细胞的促炎作用。本课题可能为AIH的炎症机制和治疗提供新的补充，并提出以ThPok为靶点的新型免疫治疗策略。

中文关键词： 自身免疫性肝病；NKT细胞；转录因子；细胞因子；免疫治疗

英文摘要： Although autoimmune hepatitis (AIH) is a kind of inflammatory liver disease of unknown etiology, iNKT cells are indispensable for the development of AIH，accordingly, there is a strong possibility that the regulation of iNKT cell function will be of great significance for the control of autoimmune hepatitis . ThPok，as a CD4 + T cell-specific transcription factor，is capable of regulating the directional differentiation of CD4 + T cells, but the role of ThPok in the regulation of iNKT cells is not fully understood . Our past research has found that ThPok can regulate the differentiation and development of mouse iNKT cells, and thus contributing to the development and progression of autoimmune hepatitis in mice by regulating the function of iNKT cells. This project focuses on the regulation of transcription factors ThPok for human iNKT cells in AIH patients . By analyzing ThPok gene expression in the peripheral blood and liver iNKT cells of AIH patient，we relate them with the degree of liver injury in patients with AIH ; we will deeply explore the influence of ThPok on human iNKT cell function，investigate whether inhibiting the ThPok expression in human iNKT cells will be able to block the pro-inflammatory role of iNKT cells. This topic may provide new evidence for the inflammatory mechanisms and treatment of AIH , and offer novel immunotherapeutic strategies targeting ThPok .

英文关键词： autoimmune hepatitis;NKT cell;transcription factor;cytokine;immunotherapy