CD11c/EYFP transgene illuminates a discrete network of dendritic cells within the embryonic, neonatal, adult, and injured mouse brain
CD11c/EYFP transgene illuminates a discrete network of dendritic cells within the embryonic, neonatal, adult, and injured mouse brain
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DOI：
10.1002/cne.21668
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发表时间：
2008-06-10
影响因子：
2.5
通讯作者：
McEwen, Bruce S.
中科院分区：
文献类型：
--
作者：
Bulloch, Karen;Miller, Melinda M.;McEwen, Bruce S.
构建CD 11 c增强的黄色荧光蛋白（EYFP）转基因小鼠以鉴定外周中的树突状细胞（Lindquist等[20041 Nat.Immunol.5：1243-1250）。在这项研究中，我们使用这种小鼠来表征中枢神经系统内的树突状细胞。我们的解剖学结果显示，EYFP+脑树突状细胞（EYFP+ bDC）的离散群体与Mac-1，Iba-1，CD 45和F4/80的小胶质细胞免疫反应阳性，但不为NeuN，Dcx，NG 2蛋白聚糖，或GFAP的小部分共定位。通过荧光激活细胞分选（FACS）分离的EYFP+ bDC表达Itgax（CD 11 c）基因的mRNA，而EYFP+ bDC培养物的FACS分析揭示了CD 11 c蛋白的存在。光学显微镜研究表明，EYFP+ bDC存在于胚胎CNS时，血脑屏障的形成和出生后，当脑细胞适合培养。在成年雄性小鼠中，EY-FP+ bDC分布在CNS区域内显著，这些区域1）受到结构可塑性和神经发生的影响，2）接受来自外部环境的感觉和体液输入，3）缺乏血脑屏障。成人神经原性龛EYFP+ bDC的超微结构分析表明，它们接近发育中的神经元和免疫/小胶质细胞的形态特征。红藻氨酸诱导的癫痫发作显示，EYFP+ bDC对海马损伤有反应，并显示出与cfms（CSF-1 R）EGFP小鼠海马中的精氨酸激活的EGFP（+）小胶质细胞相似的形态学。总的来说，这些发现表明树突状细胞家族的一个新成员居住在异质性小胶质细胞群体。
The CD11c enhanced yellow fluorescent protein (EYFP) transgenic mouse was constructed to identify dendritic cells in the periphery (Lindquist et al. [20041 Nat. Immunol. 5:1243-1250). In this study, we used this mouse to characterize dendritic cells within the CNS. Our anatomic results showed discrete populations of EYFP+ brain dendritic cells (EYFP+ bDC) that colocalized with a small fraction of microglia immunoreactive for Mac-1, Iba-1, CD45, and F4/80 but not for NeuN, Dcx, NG2 proteoglycan, or GFAP. EYFP+ bDC, isolated by fluorescent activated cell sorting (FACS), expressed mRNA for the Itgax (CD11c) gene, whereas FACS anlaysis of EYFP+ bDC cultures revealed the presence of CD11c protein. Light microscopy studies revealed that EYFP+ bDC were present in the embryonic CNS when the blood-brain barrier is formed and postnatally when brain cells are amenable to culturing. In adult male mice, EY-FP+ bDC distribution was prominent within regions of the CNS that 1) are subject to structural plasticity and neurogenesis, 2) receive sensory and humoral input from the external environment, and 3) lack a blood-brain barrier. Ultrastructural analysis of EYFP+ bDC in adult neurogenic niches showed their proximity to developing neurons and a morphology characteristic of immune/microglia cells. Kainic acid-induced seizures revealed that EYFP+ bDC responded to damage of the hippocampus and displayed morphologies similar to those described for seizure-activated EGFP(+) microglia in the hippocampus of cfms (CSF-1R) EGFP mice. Collectively, these findings suggest a new member of the dendritic cell family residing among the heterogeneous microglia population.