Galectin-9 induces maturation of human monocyte-derived dendritic cells
Galectin-9 induces maturation of human monocyte-derived dendritic cells
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DOI：
10.4049/jimmunol.175.5.2974
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发表时间：
2005-09-01
影响因子：
4.4
通讯作者：
Hirashima, M
中科院分区：
文献类型：
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作者：
Dai, SY;Nakagawa, R;Hirashima, M
树突状细胞（DC）的成熟是启动免疫应答的关键，并受到各种刺激信号的调节。我们评估了半乳糖凝集素（Gal）9在DC成熟中的作用。用外源性Gal-9培养未成熟DC以剂量依赖性方式显著增加CD 40、CD 54、CD 80、CD 83、CD 86和HLA-DR的表面表达，尽管Gal-9对人单核细胞向未成熟DC的分化没有或几乎没有影响。Gal-9处理的DC分泌IL-12但不分泌IL-10，并且它们诱导同种异体CD 4（+）T细胞产生Th 1细胞因子（IFN-γ和IL-2），但不诱导Th 2细胞因子（IL-4和IL-5）。Gal-9对未成熟DC的这些作用基本上不依赖于其凝集素性质，因为它们仅被乳糖轻微抑制。我们进一步发现，缺乏β-半乳糖苷结合活性的Gal-9突变体再现了上述活性，并且抗Gal-9 mAb抑制了它们。Gal-9诱导DCs中MAPK p38和ERK 12的磷酸化，并且p38信号传导的抑制剂，但不是ERK 12或PI 3 K信号传导的抑制剂，阻断Gal-9诱导的共刺激分子表达和IL-12产生的上调。这些发现表明，Gal-9不仅在先天免疫中起作用，而且通过诱导DC成熟和促进Th 1免疫应答在获得性免疫中起作用。
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 P-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.