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Dev Cell ; 55(5): 617-628.e6, 2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-33038331

RESUMO

The choroid plexus (ChP) regulates brain development by secreting instructive cues and providing a protective brain barrier. Here, we show that polyI:C-mediated maternal immune activation leads to an inflammatory response in the developing embryonic mouse brain that manifests as pro-inflammatory cerebrospinal fluid (CSF) and accumulation of ChP macrophages. Elevation of CSF-CCL2 was sufficient to drive ChP immune cell recruitment, activation, and proliferation. In addition, ChP macrophages abandoned their regular tiling pattern and relocated to the ChP-free margin where they breached the weakened epithelial barrier. We further found that these immune cells entered from the ChP into the brain via anatomically specialized "hotspots" at the distal tips of ChP villi. In vivo two-photon imaging demonstrated that surveillance behaviors in ChP macrophages had already emerged at this early stage of embryogenesis. Thus, the embryonic ChP forms a functional brain barrier that can mount an inflammatory response to external insults.


Assuntos
Plexo Corióideo/embriologia , Plexo Corióideo/imunologia , Inflamação/patologia , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Proliferação de Células , Líquido Cefalorraquidiano/metabolismo , Quimiocina CCL2/metabolismo , Imageamento Tridimensional , Mediadores da Inflamação/metabolismo , Ativação de Macrófagos , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/metabolismo , Receptores CCR2/metabolismo , Transdução de Sinais , Junções Íntimas/metabolismo , Regulação para Cima
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