CD318通过调节T细胞迁移与分化参与青光眼发病的免疫机制研究

青光眼是一种视神经慢性退行性疾病，是全世界致盲的主要原因之一，但发病机制（尤其免疫因素的影响）尚不明确。视网膜及外周固有免疫细胞在青光眼发病中发挥了重要作用，近年T细胞在疾病中的作用也日益被重视，但具体机制的免疫调控功能尚不清楚。我们前期发现青光眼小鼠视网膜节细胞周围出现CD6+T细胞浸润，IL-17A、TNF-α等表达水平显著升高，并发现CD318在炎性条件下在视网膜血管内皮细胞表达上调。我们推测青光眼视网膜异常表达CD318，介导CD6+T细胞迁移进入视网膜，同时诱导这些T细胞向Th1/Th17方向分化，进而参与调解局部固有免疫应答、导致节细胞损伤。本项目拟通过检测青光眼患者及小鼠CD6、CD318表达水平及定位情况、明确二者对T细胞功能的影响，并使用CD318KO小鼠明确CD6-CD318在青光眼神经损伤中的免疫调控功能。通过本研究，可能为青光眼发病机制研究提供新的思路。

Glaucoma is a chronic neurodegenerative disease of retina and optic nerve, which is one of the main causes of blindness worldwide. The pathogenesis of glaucoma, especially the immune factors, is still unclear. It has been well-documented that retinal and peripheral innate immune cells (such as microglia and monocyte) play a vital role in the pathogenesis of glaucoma, and the role of T cells in the disease has been increasingly recognized in recent years. However, the potential mechanism of how T cells regulate in the induction and development of glaucoma is still unclear. We found that CD6+ T cells were co-localized with ganglion cells during glaucoma, and retinal IL-17A and TNF-α expression was significantly increased, and CD318 expression was induced by IL-17A and TNF-α. Based on these evidences, we speculated that the abnormal expression of CD318 in glaucoma retina might contribute to mediating the migration of CD6+ T cells into the retina and facilitating the differentiation of these T cells toward Th1/Th17 lineages, thus participating in the modulation of retinal innate immune responses, leading to ganglion cell injury. In this study, we will examine the expression levels and localization of CD6 and CD318 in patients with glaucoma and mouse glaucoma model. Furthermore, we will investigate the influence of the CD6-CD318 axis on T-cell migration and function, and employ CD318 KO mice to reveal the mechanism of how CD6-CD318 axis affects retinal neuron injury during glaucoma. This study may provide new insights into the pathogenesis of glaucoma.