Journal article
Gatekeeper role of brain antigen-presenting CD11c(+) cells in neuroinflammation
EMBO Journal, Vol.35(1), pp.89-101
Jan/2016
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.
Details
- Title
- Gatekeeper role of brain antigen-presenting CD11c(+) cells in neuroinflammation
- Creators
- Magdalena Paterka (null)Volker Siffrin (null)Jan O. Voss (null)Johannes Werr (null)Nicola Hoppmann (null)Rene Gollan (null)Patrick Belikan (null)Julia Bruttger (null)Jerome Birkenstock (null)Steffen Jung (null) - 972WIS_INST___120Enric Esplugues (null)Nir Yogev (null)Richard A. Flavell (null)Tobias Bopp (null)Frauke Zipp (null)
- Resource Type
- Journal article
- Publication Details
- EMBO Journal, Vol.35(1), pp.89-101; Jan/2016
- Number of pages
- 13
- Language
- English
- DOI
- https://doi.org/10.15252/embj.201591488
- Grant note
- German Research Council (DFG); [CRC-TR-128]This work was supported by grants from the German Research Council (DFG) and to F.Z./T.B. (CRC-TR-128, B4) and to V.S. (CRC-TR-128, B9). Furthermore, we thank Christin Lieflander, Andreas Zymny, and Heike Ehrengard for expert technical assistance and Darragh O'Neill for proofreading the manuscript._ALMAME_DELIMITER_
- Record Identifier
- 993267831303596
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