Galectin-9 Induces Maturation of Human Monocyte-derived Dendritic Cells

  • YAMAUCHI Akira
    Department of Cell Regulation, Faculty of Medicine, Kagawa University
  • DAI Shu-Yan
    Department of Immunology and Immunopathology, Faculty of Medicine, Kagawa University
  • NAKAGAWA Ryusuke
    Department of Cell Regulation, Faculty of Medicine, Kagawa University
  • KASHIO Yumiko
    Department of Immunology and Immunopathology, Faculty of Medicine, Kagawa University
  • ABE Hiroko
    Department of Cell Regulation, Faculty of Medicine, Kagawa University
  • KATOH Shigeki
    Department of Cell Regulation, Faculty of Medicine, Kagawa University
  • KONTANI Keiichi
    Department of Second Department of Surgery, Faculty of Medicine, Kagawa University
  • HIRASHIMA Mitsuomi
    Department of Immunology and Immunopathology, Faculty of Medicine, Kagawa University

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Other Title
  • 糖鎖結合蛋白ガレクチン9による樹状細胞成熟化

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Abstract

  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-γ 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 β-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.<br>

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