Departments of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Eur J Immunol. 2010 Feb;40(2):548-58. doi: 10.1002/eji.200939886.
Galectin-9 (Gal-9) plays pivotal roles in the modulation of innate and adaptive immunity to suppress T-cell-mediated autoimmune models. However, it remains unclear if Gal-9 plays a suppressive role for T-cell function in non-autoimmune disease models. We assessed the effects of Gal-9 on experimental hypersensitivity pneumonitis induced by Trichosporon asahii. When Gal-9 was given subcutaneously to C57BL/6 mice at the time of challenge with T. asahii, it significantly suppressed T. asahii-induced lung inflammation, as the levels of IL-1, IL-6, IFN-gamma, and IL-17 were significantly reduced in the BALF of Gal-9-treated mice. Moreover, co-culture of anti-CD3-stimulated CD4 T cells with BALF cells harvested from Gal-9-treated mice on day 1 resulted in diminished CD4 T-cell proliferation and decreased levels of IFN-gamma and IL-17. CD11b(+)Ly-6C(high)F4/80(+) BALF Mphi expanded by Gal-9 were responsible for the suppression. We further found in vitro that Gal-9, only in the presence of T. asahii, expands CD11b(+)Ly-6C(high)F4/80(+) cells from BM cells, and the cells suppress T-cell proliferation and IFN-gamma and IL-17 production. The present results indicate that Gal-9 expands immunosuppressive CD11b(+)Ly-6C(high) Mphi to ameliorate Th1/Th17 cell-mediated hypersensitivity pneumonitis.
半乳糖凝集素-9（Gal-9）在调节先天和适应性免疫以抑制 T 细胞介导的自身免疫模型中发挥关键作用。然而，Gal-9 是否在非自身免疫疾病模型中对 T 细胞功能发挥抑制作用仍不清楚。我们评估了 Gal-9 对曲霉菌诱导的实验性过敏性肺炎的影响。当 Gal-9 在挑战曲霉菌时皮下给予 C57BL/6 小鼠时，它显著抑制了曲霉菌诱导的肺部炎症，因为 Gal-9 处理小鼠的 BALF 中 IL-1、IL-6、IFN-γ 和 IL-17 的水平显著降低。此外，在第 1 天用 Gal-9 处理的小鼠的 BALF 细胞共培养抗 CD3 刺激的 CD4 T 细胞导致 CD4 T 细胞增殖减少和 IFN-γ 和 IL-17 水平降低。Gal-9 扩增的 CD11b(+)Ly-6C(high)F4/80(+)BALF Mphi 负责抑制作用。我们进一步发现，体外 Gal-9 仅在存在曲霉菌的情况下，从 BM 细胞中扩增 CD11b(+)Ly-6C(high)F4/80(+)细胞，并且这些细胞抑制 T 细胞增殖和 IFN-γ 和 IL-17 的产生。这些结果表明，Gal-9 扩增免疫抑制性 CD11b(+)Ly-6C(high)Mphi 可改善 Th1/Th17 细胞介导的过敏性肺炎。
