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Dev Cell ; 55(5): 617-628.e6, 2020 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-33038331

RESUMEN

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.


Asunto(s)
Plexo Coroideo/embriología , Plexo Coroideo/inmunología , Inflamación/patología , Animales , Proteínas de Unión al Calcio/metabolismo , Proliferación Celular , Líquido Cefalorraquídeo/metabolismo , Quimiocina CCL2/metabolismo , Imagenología Tridimensional , Mediadores de Inflamación/metabolismo , Activación de Macrófagos , Ratones Endogámicos C57BL , Proteínas de Microfilamentos/metabolismo , Receptores CCR2/metabolismo , Transducción de Señal , Uniones Estrechas/metabolismo , Regulación hacia Arriba
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