Dando Samantha J, Naranjo Golborne Cecilia, Chinnery Holly R, Ruitenberg Marc J, McMenamin Paul G
Department of Anatomy and Developmental Biology and Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Department of Optometry and Vision Sciences, University of Melbourne, Parkville, Victoria, Australia.
Glia. 2016 Aug;64(8):1331-49. doi: 10.1002/glia.23005. Epub 2016 May 18.
Under steady-state conditions the central nervous system (CNS) is traditionally thought to be devoid of antigen presenting cells; however, putative dendritic cells (DCs) expressing enhanced yellow fluorescent protein (eYFP) are present in the retina and brain parenchyma of CD11c-eYFP mice. We previously showed that these mice carry the Crb1(rd8) mutation, which causes retinal dystrophic lesions; therefore we hypothesized that the presence of CD11c-eYFP(+) cells within the CNS may be due to pathology associated with the Crb1(rd8) mutation. We generated CD11c-eYFP Crb1(wt/wt) mice and compared the distribution and immunophenotype of CD11c-eYFP(+) cells in CD11c-eYFP mice with and without the Crb1(rd8) mutation. The number and distribution of CD11c-eYFP(+) cells in the CNS was similar between CD11c-eYFP Crb1(wt/wt) and CD11c-eYFP Crb1(rd8/rd8) mice. CD11c-eYFP(+) cells were distributed throughout the inner retina, and clustered in brain regions that receive input from the external environment or lack a blood-brain barrier. CD11c-eYFP(+) cells within the retina and cerebral cortex of CD11c-eYFP Crb1(wt/wt) mice expressed CD11b, F4/80, CD115 and Iba-1, but not DC or antigen presentation markers, whereas CD11c-eYFP(+) cells within the choroid plexus and pia mater expressed CD11c, I-A/I-E, CD80, CD86, CD103, DEC205, CD8α and CD135. The immunophenotype of CD11c-eYFP(+) cells and microglia within the CNS was similar between CD11c-eYFP Crb1(wt/wt) and CD11c-eYFP Crb1(rd8/rd8) mice; however, CD11c and I-A/I-E expression was significantly increased in CD11c-eYFP Crb1(rd8/rd8) mice. This study demonstrates that the overwhelming majority of CNS CD11c-eYFP(+) cells do not display the phenotype of DCs or their precursors and are most likely a subpopulation of microglia. GLIA 2016. GLIA 2016;64:1331-1349.
在稳态条件下，传统观点认为中枢神经系统（CNS）缺乏抗原呈递细胞；然而，在CD11c-eYFP小鼠的视网膜和脑实质中存在表达增强型黄色荧光蛋白（eYFP）的假定树突状细胞（DCs）。我们之前表明这些小鼠携带Crb1(rd8)突变，该突变会导致视网膜营养不良性病变；因此我们推测中枢神经系统中CD11c-eYFP(+)细胞的存在可能是由于与Crb1(rd8)突变相关的病理状态。我们培育了CD11c-eYFP Crb1(wt/wt)小鼠，并比较了有和没有Crb1(rd8)突变的CD11c-eYFP小鼠中CD11c-eYFP(+)细胞的分布和免疫表型。CD11c-eYFP Crb1(wt/wt)小鼠和CD11c-eYFP Crb1(rd8/rd8)小鼠中枢神经系统中CD11c-eYFP(+)细胞的数量和分布相似。CD11c-eYFP(+)细胞分布于整个视网膜内层，并聚集在接受来自外部环境输入或缺乏血脑屏障的脑区。CD11c-eYFP Crb1(wt/wt)小鼠视网膜和大脑皮质中的CD11c-eYFP(+)细胞表达CD11b、F4/80、CD115和Iba-1，但不表达DC或抗原呈递标志物，而脉络丛和软脑膜中的CD11c-eYFP(+)细胞表达CD11c、I-A/I-E、CD80、CD86、CD103、DEC205、CD8α和CD135。CD11c-eYFP Crb1(wt/wt)小鼠和CD11c-eYFP Crb1(rd8/rd8)小鼠中枢神经系统中CD11c-eYFP(+)细胞和小胶质细胞的免疫表型相似；然而，CD11c-eYFP Crb1(rd8/rd8)小鼠中CD11c和I-A/I-E的表达显著增加。这项研究表明，中枢神经系统中绝大多数CD11c-eYFP(+)细胞不表现出DC或其前体细胞的表型，很可能是小胶质细胞的一个亚群。《胶质细胞》2016年。《胶质细胞》2016；64:1331 - 1349。
