1. Gatekeeper role of brain antigen-presenting CD11c+ cells in neuroinflammation.
- Author
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Paterka M, Siffrin V, Voss JO, Werr J, Hoppmann N, Gollan R, Belikan P, Bruttger J, Birkenstock J, Jung S, Esplugues E, Yogev N, Flavell RA, Bopp T, and Zipp F
- Subjects
- Animals, Antigen-Presenting Cells chemistry, Brain immunology, Cell Movement, Dendritic Cells chemistry, Encephalomyelitis, Autoimmune, Experimental immunology, Granulocyte-Macrophage Colony-Stimulating Factor metabolism, Interleukin-17 metabolism, Mice, Inbred C57BL, T-Lymphocytes physiology, Th17 Cells physiology, Antigen-Presenting Cells physiology, Brain pathology, CD11c Antigen analysis, Dendritic Cells physiology, Encephalomyelitis, Autoimmune, Experimental pathology, T-Lymphocytes immunology
- 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., (© 2015 The Authors.)
- Published
- 2016
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