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

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.

Source: EMBO Journal - January 3, 2016 Category: Molecular Biology Authors: 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., Zipp, F. Tags: Immunology, Neuroscience Articles Source Type: research