Gatekeeper role of brain antigen-presenting CD11c+ cells in neuroinflammation

Multiple sclerosis is the most frequent chronic inflammatory disease of the CNS. The entry and survival of pathogenic T cells in the CNS are crucial for the initiation and persistence of autoimmune neuroinflammation. In this respect, contradictory evidence exists on the role of the most potent type of antigen‐presenting cells, dendritic cells. Applying intravital two‐photon microscopy, we demonstrate the gatekeeper function of CNS professional antigen‐presenting CD11c + cells, which preferentially interact with Th17 cells. IL‐17 expression correlates with expression of GM‐CSF by T cells and with accumulation of CNS CD11c + cells. These CD11c + cells are organized in perivascular clusters, targeted by T cells, and strongly express the inflammatory chemokines Ccl5 , Cxcl9 , and Cxcl10 . Our findings demonstrate a fundamental role of CNS CD11c + cells in the attraction of pathogenic T cells into and their survival within the CNS. Depletion of CD11c + cells markedly reduced disease severity due to impaired enrichment of pathogenic T cells within the CNS. Synopsis Brain antigen‐presenting CD11c + cells play a fundamental role in the attraction of pathogenic T cells into and their survival within the CNS, critically influencing the immune response in neuroinflammation. Investigation of role of CNS CD11c + cells using experimental autoimmune encephalomyelitis in CD11c‐DTR/GFP transgenic mouse model and two‐photon laser‐scanning microscopy. IL‐17 expression correlates with GM‐CSF expression by T cells and with accumulation of CD11c + cells. Accumulated CD11c + cells organize in perivascular clusters and strongly express the inflammatory chemokines Ccl5 , Cxcl9 , and Cxcl10 . Depletion of CD11c + cells reduced the encephalitogenicity of adoptively transferred T cells in CNS and thus markedly reduced EAE disease severity. Graphical Abstract Specific dendritic cells are fundamental for attracting autoinflammatory Th17 cells to the central nervous system in chronic autoimmune diseases.