Flt3L controls the development of radiosensitive dendritic cells in the meninges and choroid plexus of the steady-state mouse brain.

Flt3L controls the development of radiosensitive dendritic cells in the meninges and choroid plexus of the steady-state mouse brain.
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DOI:
10.1084/jem.20102657
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发表时间:
2011-08-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Liu K
Liu K
中科院分区:
其他
文献类型:
--
作者:
Anandasabapathy N;Victora GD;Meredith M;Feder R;Dong B;Kluger C;Yao K;Dustin ML;Nussenzweig MC;Steinman RM;Liu K

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如通过形态学、基因表达、抗原呈递功能和Flt 3依赖性的分析所示,稳态小鼠脑包含与脾DC具有相似性而与小胶质细胞具有差异的DC群体。无病脑中的抗原呈递细胞主要通过抗原如CD 11b、CD 11 c和MHC II的表达来鉴定,这些抗原可由树突状细胞(DC)、小胶质细胞和单核细胞共享。在这项研究中,从Flt 3(FMS样受体酪氨酸激酶3)依赖性发展的标准,我们的特点,真正的DC在健康小鼠脑内的脑膜和脉络丛。形态学,基因表达和抗原呈递功能的分析建立了脑膜和脉络丛DC(m/chDC)和脾脏DC之间的密切关系。两个位点中的DC对Flt 3配体具有内在需求。微阵列显示,与单核细胞和小胶质细胞相比,m/chDCs中编码表面分子、转录因子、模式识别受体和其他基因的转录本表达存在差异。来自骨髓的迁移前DC祖细胞产生具有5-7-d半衰期的m/chDC。与小胶质细胞相反,DC主动呈递自身抗原并刺激T细胞。因此,稳定状态脑的脑膜和脉络丛含有源自局部前体的DC,并且表现出与脾DC相似且不同于小胶质细胞的分化和抗原呈递程序。
As shown by analyses of morphology, gene expression, antigen-presenting function, and Flt3 dependence, the steady-state mouse brain contains a population of DCs that exhibits similarities to splenic DCs and differences from microglia. Antigen-presenting cells in the disease-free brain have been identified primarily by expression of antigens such as CD11b, CD11c, and MHC II, which can be shared by dendritic cells (DCs), microglia, and monocytes. In this study, starting with the criterion of Flt3 (FMS-like receptor tyrosine kinase 3)-dependent development, we characterize the features of authentic DCs within the meninges and choroid plexus in healthy mouse brains. Analyses of morphology, gene expression, and antigen-presenting function established a close relationship between meningeal and choroid plexus DCs (m/chDCs) and spleen DCs. DCs in both sites shared an intrinsic requirement for Flt3 ligand. Microarrays revealed differences in expression of transcripts encoding surface molecules, transcription factors, pattern recognition receptors, and other genes in m/chDCs compared with monocytes and microglia. Migrating pre-DC progenitors from bone marrow gave rise to m/chDCs that had a 5–7-d half-life. In contrast to microglia, DCs actively present self-antigens and stimulate T cells. Therefore, the meninges and choroid plexus of a steady-state brain contain DCs that derive from local precursors and exhibit a differentiation and antigen-presenting program similar to spleen DCs and distinct from microglia.
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