Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France.
Université de Tours, Inserm, N2C UMR 1069, Faculté de Médecine, Tours, France.
Front Immunol. 2020 Jan 8;10:3032. doi: 10.3389/fimmu.2019.03032. eCollection 2019.
CD36, a member of the class B scavenger receptor family, participates in Toll-like receptor signaling on mononuclear phagocytes (MP) and can promote sterile pathogenic inflammation. We here analyzed the effect of CD36 deficiency on retinal inflammation and photoreceptor degeneration, the hallmarks of age-related macular degeneration (AMD), that characterize mice. We analyzed subretinal MP accumulation, and cone- and rod-degeneration in light-challenged and aged, CD36 competent or deficient, hyper-inflammatory mice, using histology and immune-stained retinal flatmounts. Monocytes (Mo) were subretinally adoptively transferred to evaluate their elimination rate from the subretinal space and Interleukin 6 (IL-6) secretion from cultured Mo-derived cells (MdCs) of the different mouse strains were analyzed. CD36 deficient mice were protected against age- and light-induced subretinal inflammation and associated cone and rod degeneration. CD36 deficiency in MPs inhibited their prolonged survival in the immune-suppressive subretinal space and reduced the exaggerated IL-6 secretion observed in MPs that we previously showed leads to increased subretinal MP survival. deficiency significantly protected hyperinflammatory mice against subretinal MP accumulation and associated photoreceptor degeneration. The observed CD36-dependent induction of pro-inflammatory IL-6 might be at least partially responsible for the prolonged MP survival in the immune-suppressive environment and its pathological consequences on photoreceptor homeostasis.
CD36 是 B 族清道夫受体家族的成员，它参与单核吞噬细胞（MP）中的 Toll 样受体信号转导，并能促进无菌性致病炎症。我们在此分析了 CD36 缺失对视网膜炎症和光感受器变性的影响，这是年龄相关性黄斑变性（AMD）的标志。我们使用组织学和免疫染色视网膜平面标本分析了光应激和老化的 CD36 功能正常和缺失的高炎症性小鼠中的视网膜下 MP 积累以及视锥和视杆变性。通过视网膜下过继转移单核细胞（Mo）来评估不同小鼠品系的 Mo 从视网膜下空间的消除率和培养的 Mo 衍生细胞（MdCs）中白细胞介素 6（IL-6）的分泌。CD36 缺失的小鼠对年龄和光诱导的视网膜下炎症以及相关的视锥和视杆变性具有保护作用。MP 中的 CD36 缺失抑制了它们在免疫抑制性视网膜下空间中的延长存活，并减少了我们之前发现的导致视网膜下 MP 存活增加的 MP 中过度分泌的白细胞介素 6（IL-6）。CD36 缺失显著保护高炎症性小鼠免受视网膜下 MP 积累和相关光感受器变性的影响。观察到的 CD36 依赖性诱导的促炎白细胞介素 6 可能至少部分负责在免疫抑制环境中延长 MP 的存活及其对光感受器稳态的病理后果。
