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

The EMBO journal 2016 Jan 04

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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. © 2015 The Authors.

Citation

Magdalena Paterka, Volker Siffrin, Jan O Voss, Johannes Werr, Nicola Hoppmann, René Gollan, Patrick Belikan, Julia Bruttger, Jérôme Birkenstock, Steffen Jung, Enric Esplugues, Nir Yogev, Richard A Flavell, Tobias Bopp, Frauke Zipp. Gatekeeper role of brain antigen-presenting CD11c+ cells in neuroinflammation. The EMBO journal. 2016 Jan 04;35(1):89-101