Retinal microglia initiate neuroinflammation in ocular autoimmunity
Retinal microglia initiate neuroinflammation in ocular autoimmunity
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DOI：
10.1073/pnas.1820387116
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发表时间：
2019-05-14
影响因子：
11.1
通讯作者：
Connor, Kip M.
中科院分区：
文献类型：
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作者：
Okunuki, Yoko;Mukai, Ryo;Connor, Kip M.
自身免疫性葡萄膜炎是一种威胁视力的眼部炎症状态，视网膜和葡萄膜组织成为自身反应性免疫细胞的靶点。虽然小胶质细胞在自身免疫性葡萄膜炎中得到了广泛的研究，但其确切功能仍不确定。本研究的目的是确定在自身免疫性葡萄膜炎中驻留的小胶质细胞是否是启动和放大视网膜炎症的必要条件和充分性细胞。在这项研究中，我们利用实验性自身免疫性葡萄膜视网膜炎(EAU)的小鼠模型和最近发现的小胶质细胞特异性标记物P2ry12清楚地证明了小胶质细胞对于启动免疫细胞的渗透是必不可少的。在EAU中，小胶质细胞的主要功能是启动疾病，因为在EAU的后期阶段清除小胶质细胞效果不大，这表明一旦小胶质细胞触发疾病，循环中的白细胞的功能就是放大和维持破坏性炎症。在没有小胶质细胞的情况下，葡萄膜炎不会发生，因为白细胞不能通过血-视网膜屏障进入，这表明小胶质细胞在调节炎性细胞渗透到视网膜中起着关键作用。
Autoimmune uveitis is a sight-threatening ocular inflammatory condition in which the retina and uveal tissues become a target of autoreactive immune cells. While microglia have been studied extensively in autoimmune uveitis, their exact function remains uncertain. The objective of the current study was to determine whether resident microglia are necessary and sufficient to initiate and amplify retinal inflammation in autoimmune uveitis. In this study, we clearly demonstrate that microglia are essential for initiating infiltration of immune cells utilizing a murine model of experimental autoimmune uveoretinitis (EAU) and the recently identified microglia-specific marker P2ry12. Initiating disease is the primary function of microglia in EAU, since eliminating microglia during the later stages of EAU had little effect, indicating that the function of circulating leukocytes is to amplify and sustain destructive inflammation once microglia have triggered disease. In the absence of microglia, uveitis does not develop, since leukocytes cannot gain entry through the blood-retinal barrier, illustrating that microglia play a critical role in regulating infiltration of inflammatory cells into the retina.