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

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Item Type:	Article
Title:	Gatekeeper role of brain antigen-presenting CD11c(+) cells in neuroinflammation
Creators Name:	Paterka, M., Siffrin, V., Voss, J.O., Werr, J., Hoppmann, N., Gollan, R., Belikan, P., Bruttger, J., Birkenstock, J., Jung, S., Esplugues, E., Yogev, N., Flavell, R.A., 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
ISSN:	0261-4189
Publisher:	EMBO Press / Wiley
Volume:	35
Number:	1
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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