title: Galectin-9 induces maturation of human monocyte-derived dendritic cells.
abstract: 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.
authors.affiliation: Department of Immunology and Immunopathology, Kagawa University, Ikenobe, Miki, Japan.
authors.forename: Shu-Yan
authors.initials: SY
authors.lastname: Dai
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Nakagawa
authors.forename: Aiko
authors.initials: A
authors.lastname: Itoh
authors.forename: Hiromoto
authors.initials: H
authors.lastname: Murakami
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kashio
authors.forename: Hiroko
authors.initials: H
authors.lastname: Abe
authors.forename: Shigeki
authors.initials: S
authors.lastname: Katoh
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kontani
authors.forename: Minoru
authors.initials: M
authors.lastname: Kihara
authors.forename: Shu-Lan
authors.initials: SL
authors.lastname: Zhang
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hata
authors.forename: Takanori
authors.initials: T
authors.lastname: Nakamura
authors.forename: Akira
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Mitsuomi
authors.initials: M
authors.lastname: Hirashima
mesh_terms: D017951:Antigen Presentation; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D037161:Galectins / Q000502:physiology*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D007785:Lactose / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000166:cytology*; D010766:Phosphorylation; D018417:Th1 Cells / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D037161:Galectins; D008070:Lipopolysaccharides; D015847:Interleukin-4; D048051:p38 Mitogen-Activated Protein Kinases; D007785:Lactose