Galectin-9 induces maturation of human monocyte-derived dendritic cells.
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.
Dai
Shu-Yan
SY
Department of Immunology and Immunopathology, Kagawa University, Ikenobe, Miki, Japan.
Nakagawa
Ryusuke
R
Itoh
Aiko
A
Murakami
Hiromoto
H
Kashio
Yumiko
Y
Abe
Hiroko
H
Katoh
Shigeki
S
Kontani
Keiichi
K
Kihara
Minoru
M
Zhang
Shu-Lan
SL
Hata
Toshiyuki
T
Nakamura
Takanori
T
Yamauchi
Akira
A
Hirashima
Mitsuomi
M
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
D037161:Galectins; D008070:Lipopolysaccharides; D015847:Interleukin-4; D048051:p38 Mitogen-Activated Protein Kinases; D007785:Lactose