最近认为Th1/Th17细胞也存在相互抑制的作用，分化调节Th1细胞的主要转录因子是T-bet；而RORγt是Th17细胞分化的关键转录因子。拟采用T-bet-/-、RORγt-/- 基因敲除（KO）、RORγt-GFP（绿色荧光蛋白）和野生型（WT）的变应性鼻炎（AR）小鼠模型，针对反映鼻粘膜免疫系统的鼻相关淋巴组织（NALT），研究AR中T-bet对RORγt介导的Th17细胞反应负调控作用和机制。运用T细胞极化、RT-PCR、流式细胞术、Transwell实验、细胞过继性转移等方法，研究上述AR模型中Th17细胞反应、T-bet表达对Th17分化的抑制作用、变应原诱导的鼻粘膜炎症变化,以及过继转移的缺乏T-bet 的T细胞对Th17细胞反应动力学的影响。了解T-bet的各种介导途径对Th17细胞粘膜局部免疫反应的影响特点。为探究抑制RORγt是否可成为AR靶向治疗的切入点提供资料。

Th1/Th17 cell mutually inhibition has been considered recently. T-bet is a main transcription factor to control differentiation of Th1 cells and RORγt is a key transcription factor to effect the differentiation of Th17 cells. We study the negative regulatory effect and its mechanisms of T-bet on RORγt-mediated Th17 cell responses in allergic rhinitis (AR) by the use of nasal-associated lymphoid tissue (NALT), which responses for nasal immune system response, from AR model mice with knock-out T-bet -/-, RORγt -/- , RORγt-GFP (green fluorescent protein) and wild type(WT). By the methods such as T cell polarization, RT-PCR, flow cytometry, Transwell experiments, cell adoptive transfer and so on, we investigate Th17 cell response and the inhibition of differentiation of Th17 caused by T-bet expression, including allergen-induced changes of nasal inflammation in above AR models. It will be detected of the kinetics effects of Th17 response by adoptive transfer of T-bet -/- T cells. To understand local mucosa immune response characterized by Th17 cells under the various T-bet-mediated pathways. It may be provided that inhibition of RORγt could become the starting point of the target treatment of AR.