[Galectin-9 induces maturation of human monocyte-derived dendritic cells].
We investigated the role of galectin-9 (Gal-9) in maturation of dendritic cells (DC). Culture of immature DCs with exogenous Gal-9 markedly increased the surface expression of CD40, CD54, CD80, CD83, CD86, and HLA-DR in a concentration-dependent manner, although Gal-9 had no 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 only slightly inhibited 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 p38 MAPK and ERK1/2 in DCs, and an inhibitor of p38 signaling, but not inhibitors of signaling by either ERK1/2 or phosphatidylinositol 3-kinase, 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.
Yamauchi
Akira
A
Department of Cell Regulation, Faculty of Medicine, Kagawa University.
Dai
Shu-Yan
SY
Nakagawa
Ryusuke
R
Kashio
Yumiko
Y
Abe
Hiroko
H
Katoh
Shigeki
S
Kontani
Keiichi
K
Hirashima
Mitsuomi
M
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D037161:Galectins / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000378:metabolism
D015703:Antigens, CD; D016207:Cytokines; D037161:Galectins; C105032:LGALS9 protein, human; D018664:Interleukin-12