Gatekeeper role of brain antigen-presenting CD11c+ cells in neuroinflammation.
EMBO J
; 35(1): 89-101, 2016 Jan 04.
Article
en En
| MEDLINE
| ID: mdl-26612827
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Encéfalo
/
Linfocitos T
/
Antígeno CD11c
/
Encefalomielitis Autoinmune Experimental
/
Células Presentadoras de Antígenos
Límite:
Animals
Idioma:
En
Año:
2016
Tipo del documento:
Article