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Galectin-9 induces maturation of human monocyte-derived dendritic cells.
J Immunol ; 175(5): 2974-81, 2005 Sep 01.
Article en En | MEDLINE | ID: mdl-16116184
Maturation of dendritic cells (DCs) is critical for initiation of immune responses and is regulated by various stimulatory signals. We assessed the role of galectin (Gal)-9 in DC maturation. Culture of immature DCs with exogenous Gal-9 markedly increased the surface expression of CD40, CD54, CD80, CD83, CD86, and HLA-DR in a dose-dependent manner, although Gal-9 had no or little effect on differentiation of human monocytes into immature DCs. Gal-9-treated DCs secreted IL-12 but not IL-10, and they elicited the production of Th1 cytokines (IFN-gamma and IL-2) but not that of the Th2 cytokines (IL-4 and IL-5) by allogeneic CD4+ T cells. These effects of Gal-9 on immature DCs were not essentially dependent on its lectin properties, given that they were inhibited only slightly by lactose. We further found that a Gal-9 mutant that lacks beta-galactoside binding activity reproduced the above activities and that an anti-Gal-9 mAb suppressed them. Gal-9 induced phosphorylation of the MAPK p38 and ERK1/2 in DCs, and an inhibitor of p38 signaling, but not inhibitors of signaling by either ERK1/2 or PI3K, blocked Gal-9-induced up-regulation of costimulatory molecule expression and IL-12 production. These findings suggest that Gal-9 plays a role not only in innate immunity but also in acquired immunity by inducing DC maturation and promoting Th1 immune responses.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Monocitos / Galectinas Límite: Humans Idioma: En Revista: J Immunol Año: 2005 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Monocitos / Galectinas Límite: Humans Idioma: En Revista: J Immunol Año: 2005 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos