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

Item Type:Article
Title:Gatekeeper role of brain antigen-presenting CD11c(+) cells in neuroinflammation
Creators Name:Paterka, M. and Siffrin, V. and Voss, J.O. and Werr, J. and Hoppmann, N. and Gollan, R. and Belikan, P. and Bruttger, J. and Birkenstock, J. and Jung, S. and Esplugues, E. and Yogev, N. and Flavell, R.A. and Bopp, T. and Zipp, F.
Abstract: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.
Keywords:Chemokines, Dendritic Cells, EAE/MS, Th17, Two-Photon Microscopy, Animals, Mice
Source:EMBO Journal
Publisher:EMBO Press / Wiley
Page Range:89-101
Date:4 January 2016
Official Publication:https://doi.org/10.15252/embj.201591488
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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