Dendritic Cells and Microglia Have Non-redundant Functions in the Inflamed Brain with Protective Effects of Type 1 cDCs

树突状细胞和小胶质细胞在发炎的大脑中具有非冗余功能,并具有 1 型 cDC 的保护作用

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作者:Mattia Gallizioli, Francesc Miró-Mur, Amaia Otxoa-de-Amezaga, Roger Cugota, Angélica Salas-Perdomo, Carles Justicia, Vanessa H Brait, Francisca Ruiz-Jaén, Maria Arbaizar-Rovirosa, Jordi Pedragosa, Ester Bonfill-Teixidor, Mathias Gelderblom, Tim Magnus, Eva Cano, Carlos Del Fresno, David Sancho, Anna

Abstract

Brain CD11c+ cells share features with microglia and dendritic cells (DCs). Sterile inflammation increases brain CD11c+ cells, but their phenotype, origin, and functions remain largely unknown. We report that, after cerebral ischemia, microglia attract DCs to the inflamed brain, and astroglia produce Flt3 ligand, supporting development and expansion of CD11c+ cells. CD11c+ cells in the inflamed brain are a complex population derived from proliferating microglia and infiltrating DCs, including a major subset of OX40L+ conventional cDC2, and also cDC1, plasmacytoid, and monocyte-derived DCs. Despite sharing certain morphological features and markers, CD11c+ microglia and DCs display differential expression of pattern recognition receptors and chemokine receptors. DCs excel CD11c- and CD11c+ microglia in the capacity to present antigen through MHCI and MHCII. Of note, cDC1s protect from brain injury after ischemia. We thus reveal aspects of the dynamics and functions of brain DCs in the regulation of inflammation and immunity.

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