Constitutive retinal CD200 expression regulates resident microglia and activation state of inflammatory cells during experimental autoimmune uveoretinitis
Constitutive retinal CD200 expression regulates resident microglia and activation state of inflammatory cells during experimental autoimmune uveoretinitis
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DOI：
10.1016/s0002-9440(10)64444-6
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发表时间：
2002-11-01
影响因子：
6
通讯作者：
Dick, AD
中科院分区：
文献类型：
--
作者：
Broderick, C;Hoek, RM;Dick, AD
最近的证据支持组织 OX2 (CD200) 通过 CD200 受体 (CD200R) 向髓系细胞组成型提供下调信号的观点。因此，缺乏CD200（CD200(-/-)）的小鼠表现出对组织特异性自身免疫的易感性增加并加速发生。在视网膜中，CD200在神经元和视网膜血管内皮上广泛表达。我们在此表明，CD200（-/-）小鼠的视网膜小胶质细胞表现出正常的形态，但与野生型CD200（+/+）小鼠的小胶质细胞不同，其数量增加，最显着的是，表达诱导型一氧化氮合酶（NOS2），这是一种巨噬细胞激活标记。在CD200(-/-)小鼠中，光感受器间视黄醇结合蛋白诱导的实验性自身免疫性葡萄膜视网膜炎的葡萄膜形成肽(1-20)的发病和严重程度加速，尽管组织破坏似乎不比CD200(+/+)小鼠中所见的更大，但神经节和光感受器细胞凋亡持续增加。在实验性自身免疫性葡萄膜视网膜炎期间，CD200(-/-)小鼠的骨髓细胞浸润增加，但NOS2表达并未升高。结果表明CD200:CD200R轴调节视网膜小胶质细胞的激活。在CD200(-/-)小鼠中，在CD200(-/-)稳态中NOS2表达增加的支持下，强直性巨噬细胞激活的抑制的释放加速了疾病的发作，但没有任何证据表明靶器官/组织破坏增加。
Recent evidence supports the notion that tissue OX2 (CD200) constitutively provides down-regulatory signals to myeloid-lineage cells via CD200-receptor (CD200R). Thus, mice lacking CD200 (CD200(-/-)) show increased susceptibility to and accelerated onset of tissue-specific autoimmunity. In the retina there is extensive expression of CD200 on neurons and retinal vascular endothelium. We show here that retinal microglia in CD200(-/-) mice display normal morphology, but unlike microglia from wild-type CD200(+/+) mice are present in increased numbers and most significantly, express inducible nitric oxide synthase (NOS2), a macrophage activation marker. Onset and severity of uveitogenic peptide (1-20) of interphotoreceptor retinoid-binding protein-induced experimental autoimmune uveoretinitis is accelerated in CD200(-/-) mice and although tissue destruction appears no greater than seen in CD200(+/+) mice, there is continued increased ganglion and photoreceptor cell apoptosis. Myeloid cell infiltrate was increased in CD200(-/-) mice during experimental autoinimune uveoretinitis, although NOS2 expression was not heightened. The results indicate that the CD200:CD200R axis regulates retinal microglial activation. In CD200(-/-) mice the release of suppression of tonic macrophage activation, supported by increased NOS2 expression in the CD200(-/-) steady state accelerates disease onset but without any demonstration of increased target organ/tissue destruction.