CD8+CD103+调节性T细胞在干眼中的免疫调控机制研究

Previous studies have demonstrated that CD8+ cell population contains regulatory cell subsets that suppress generation of the pathogenic T helper (th) 17 response that plays a pivotal role corneal barrier function disruption in dry eye. CD8+ CD103+ Treg is an important subset of CD8+ Treg. CD8+ CD103+ Tregs were noted in the mouse ocular surface, more than 60% of CD8+ lymphocytes in the cervical lymph node were found to co-express CD103, and the number of these CD8+CD103+ Tregs significantly increased in dry eye. The evidence above mentioned suggests that CD8+ CD103+ Treg may have a pivotal role in the pathogenesis of CD4+ T cell biased autoimmune diseases in dry eye; however, little is known about the regulatory effect of CD8+ CD103+ Treg in dry eye. The purpose of this study was to investigate whether CD8+ CD103+ Treg could suppress generation of CD4+ T cell, especially Th17 effector cells via activation of antigen present cell in experimental dry eye induced by desiccating stress. This study maybe provides new insight into the pathogenesis of CD4+ T cell biased autoimmune diseases in dry eye.

CD8+ 调节性T细胞（Regulatory T cell, Treg）在干眼免疫异常中起着重要的调控作用，其可显著抑制干眼致病性CD4+ T细胞，尤其是Th17细胞的增殖,并改善角膜上皮屏障功能。 CD8+ CD103+ Treg是重要的CD8+ Treg亚型，其对粘膜免疫异常具有重要的调控作用。干眼主要表现为结膜、角膜上皮等粘膜组织的免疫异常，CD8+ CD103+ Treg可能为在干眼中起主要免疫调控中作用的CD8+ Treg亚型；然而，对于CD8+ CD103+ Treg在干眼发病中的作用，目前尚无报道。本项目拟应用干燥环境诱导的小鼠干眼模型，首次系统研究CD8+ CD103+ Treg在干眼中的免疫调控作用与机制，研究CD8+ CD103+ Treg在干眼中对抗原提呈细胞激活、CD4+ T细胞增殖分化，Th炎症因子表达以及眼表上皮损害的影响。本研究有望为干眼找到新的免疫治疗靶点。

研究背景：CD8+ 调节性T细胞（Regulatory T cell, Treg）在干眼免疫异常中起着重要的调控作用，其可显著抑制干眼致病性CD4+ T细胞，尤其是Th17细胞的增殖,并改善角膜上皮屏障功能。 CD8+ CD103+ Treg是重要的CD8+ Treg亚型，其对粘膜免疫异常具有重要的调控作用。干眼主要表现为结膜、角膜上皮等粘膜组织的免疫异常，CD8+ CD103+ Treg可能为在干眼中起主要免疫调控中作用CD8+ Treg亚型；然而，对于CD8+ CD103+ Treg在干眼发病中的作用，目前尚无报道。..研究内容：本项目应用干燥环境诱导的小鼠干眼模型，研究了CD8+ CD103+ Treg在干眼中的免疫调控作用、CD4+ T细胞增殖分化，以及Th炎症因子表达的影响。..研究结果：腹腔注射CD8+CD103+Treg可以有效改善干眼小鼠泪液分泌量，提高干眼小鼠结膜杯状细胞数量，改善干眼小鼠角膜上皮屏障功能。腹腔注射CD8+CD103+Treg可以有效降低干眼小鼠角膜上皮MMP-9与MMP-3的表达。腹腔注射CD8+CD103+Treg可以有效抑制干眼小鼠结膜与颈部淋巴结CD4+T细胞浸润，降低干眼小鼠结膜与颈部淋巴结IL-17与IFN-ɤ的分泌并升高IL-13的分泌。腹腔注射CD8+CD103+Treg 可以有效抑制干眼小鼠眼表上皮细胞凋亡。..研究结论：CD8+CD103+Treg可以有效调控干眼免疫反应并改善眼表上皮损害。本研究是从一个全新的视角来研究干眼免疫反应机制，CD8+CD103+Treg有望成为干眼新的免疫治疗靶点。