视网膜色素上皮
小胶质细胞
细胞生物学
穆勒胶质细胞
生物
脉络膜
炎症
视网膜
细胞因子
重编程
视网膜
神经科学
免疫学
细胞
干细胞
祖细胞
生物化学
遗传学
作者
Yan Chen,Sarah E. Bounds,Xiang Ma,James Regun Karmoker,Yin Liu,Jian-Xing Ma,Jiyang Cai
标识
DOI:10.1073/pnas.2311647120
摘要
Injuries to the retinal pigment epithelium (RPE) and outer retina often result in the accumulation of retinal microglia within the subretinal space. These subretinal microglia play crucial roles in inflammation and resolution, but the mechanisms governing their functions are still largely unknown. Our previous research highlighted the protective functions of choroidal γδ T cells in response to RPE injury. In the current study, we employed single-cell RNA sequencing approach to characterize the profiles of immune cells in mouse choroid. We found that γδ T cells were the primary producer of interleukin-17 (IL-17) in the choroid. IL-17 signaled through its receptor on the RPE, subsequently triggering the production of interleukin-6. This cascade of cytokines initiated a metabolic reprogramming of subretinal microglia, enhancing their capacity for lipid metabolism. RPE-specific knockout of IL-17 receptor A led to the dysfunction of subretinal microglia and RPE pathology. Collectively, our findings suggest that responding to RPE injury, the choroidal γδ T cells can initiate a protective signaling cascade that ensures the proper functioning of subretinal microglia.
科研通智能强力驱动
Strongly Powered by AbleSci AI