Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Department of Ophthalmology, General Hospital of Guangzhou Military Command of PLA, Guangzhou, China; Southern Medical University, Guangzhou, China.
Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China; Southern Medical University, Guangzhou, China.
Mol Immunol. 2019 Oct;114:243-250. doi: 10.1016/j.molimm.2019.07.028. Epub 2019 Aug 5.
Age-related macular degeneration (AMD) is the most common cause of vision loss in the aged population. Aging and inflammation are thought to promote AMD pathogenesis in people with genetic predisposition. Follicular helper T (Tfh) cells play critical roles in inflammatory responses. Here, we investigated circulating Tfh cells in AMD patients. Circulating Tfh cells were defined as CXCR5 CD4 T cells. Data showed that patients with the wet-type AMD presented significantly higher levels of Tfh cells than non-AMD controls. Interestingly, the Tfh cells from dry and wet AMD patients also presented significantly higher ICOS and PD-1 expression, together with higher IL-17 and IL-21 expression directly ex vivo and following PMA/ionomycin stimulation. The expression of IFNg and IL-10, on the other hand, was not different between Tfh cells from AMD patients and their counterparts in non-AMD controls. Functional analysis revealed that Tfh cells from AMD patients were better at inducing the production of IgG and IgA, and this effect was in an IL-21-dependent manner. Together, we demonstrated that the circulating Tfh cell responses were dysregulated in AMD patients.
年龄相关性黄斑变性（AMD）是老年人群视力丧失的最常见原因。衰老和炎症被认为会促进具有遗传易感性的人发生 AMD 发病机制。滤泡辅助 T（Tfh）细胞在炎症反应中发挥关键作用。在这里，我们研究了 AMD 患者的循环 Tfh 细胞。循环 Tfh 细胞被定义为 CXCR5 CD4 T 细胞。数据显示，湿性 AMD 患者的 Tfh 细胞水平明显高于非 AMD 对照组。有趣的是，来自干性和湿性 AMD 患者的 Tfh 细胞也表现出明显更高的 ICOS 和 PD-1 表达，以及更高的 IL-17 和 IL-21 表达，直接在体外和 PMA/离子霉素刺激后。另一方面，IFNg 和 IL-10 的表达在 AMD 患者和非 AMD 对照组的 Tfh 细胞之间没有差异。功能分析表明，AMD 患者的 Tfh 细胞更擅长诱导 IgG 和 IgA 的产生，并且这种作用依赖于 IL-21。总之，我们证明了 AMD 患者的循环 Tfh 细胞反应失调。
