Artículo
Src family kinases Fyn and Lyn are constitutively activated and mediate plasmacytoid dendritic cell responses
Dallari, S.; MacAl, M.; Loureiro, Maria Eugenia
; Jo, Y.; Swanson, L.; Hesser, C.; Ghosh Roy, Prashun; Zuniga, Elina Isabel
Fecha de publicación:
04/2017
Editorial:
Nature Publishing Group
Revista:
Nature Communications
ISSN:
2041-1723
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Plasmacytoid dendritic cells (pDC) are type I interferon-producing cells with critical functions in a number of human illnesses; however, their molecular regulation is incompletely understood. Here we show the role of Src family kinases (SFK) in mouse and human pDCs. pDCs express Fyn and Lyn and their activating residues are phosphorylated both before and after Toll-like receptor (TLR) stimulation. Fyn or Lyn genetic ablation as well as treatment with SFK inhibitors ablate pDC (but not conventional DC) responses both in vitro and in vivo. Inhibition of SFK activity not only alters TLR-ligand localization and inhibits downstream signalling events, but, independent of ex-vivo TLR stimulation, also affects constitutive phosphorylation of BCAP, an adaptor protein bridging PI3K and TLR pathways. Our data identify Fyn and Lyn as important factors that promote pDC responses, describe the mechanisms involved and highlight a tonic SFK-mediated signalling that precedes pathogen encounter, raising the possibility that small molecules targeting SFKs could modulate pDC responses in human diseases.
Palabras clave:
Dendritic-Cells
,
Interferon
,
Sfk
,
Fyn-Lyn
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Identificadores
Colecciones
Articulos(ICT - MILSTEIN)
Articulos de INST.DE CS. Y TECNOLOGIA "DR. CESAR MILSTEIN"
Articulos de INST.DE CS. Y TECNOLOGIA "DR. CESAR MILSTEIN"
Citación
Dallari, S.; MacAl, M.; Loureiro, Maria Eugenia; Jo, Y.; Swanson, L.; et al.; Src family kinases Fyn and Lyn are constitutively activated and mediate plasmacytoid dendritic cell responses; Nature Publishing Group; Nature Communications; 8; 4-2017; 1-16
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