folder

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

Authors

  • M. Paterka
  • V. Siffrin
  • J.O. Voss
  • J. Werr
  • N. Hoppmann
  • R. Gollan
  • P. Belikan
  • J. Bruttger
  • J. Birkenstock
  • S. Jung
  • E. Esplugues
  • N. Yogev
  • R.A. Flavell
  • T. Bopp
  • F. Zipp

Journal

  • EMBO Journal

Citation

  • EMBO J 35 (1): 89-101

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.


DOI

doi:10.15252/embj.201591488