Galectin-9 expands immunosuppressive macrophages to ameliorate T-cell-mediated lung inflammation
Galectin-9 expands immunosuppressive macrophages to ameliorate T-cell-mediated lung inflammation
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DOI：
10.1002/eji.200939886
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发表时间：
2010-02-01
影响因子：
5.4
通讯作者：
Hirashima, Mitsuomi
中科院分区：
文献类型：
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作者：
Arikawa, Tomohiro;Saita, Naoki;Hirashima, Mitsuomi
半乳糖凝集素-9（Galectin-9，Gal-9）在调节先天性和适应性免疫以抑制T细胞介导的自身免疫模型中起关键作用。然而，尚不清楚Gal-9是否在非自身免疫性疾病模型中对T细胞功能起抑制作用。我们评估了Gal-9对由Trichosporon asahii诱导的实验性过敏性肺炎的影响。当在用Asahii攻击时向C57 BL/6小鼠皮下给予Gal-9时，其显著抑制Asahii诱导的肺部炎症，因为在Gal-9处理的小鼠的BALF中IL-1、IL-6、IFN-γ和IL-17的水平显著降低。此外，在第1天将抗CD 3刺激的CD 4 T细胞与从Gal-9处理的小鼠收获的BALF细胞共培养导致CD 4 T细胞增殖减少和IFN-γ和IL-17水平降低。CD 11b（+）Ly-6C（高）F4/80（+）BALF M（经Gal-9扩增）起抑制作用。我们进一步在体外发现，Gal-9仅在存在Tasahii的情况下从BM细胞扩增CD 11b（+）Ly-6C（高）F4/80（+）细胞，并且所述细胞抑制T细胞增殖以及IFN-γ和IL-17产生。目前的结果表明，Gal-9扩大免疫抑制性CD 11b（+）Ly-6C（高）M phi，以改善Th 1/Th 17细胞介导的过敏性肺炎。
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 I 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 M( 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) M phi to ameliorate Th1/Th17 cell-mediated hypersensitivity pneumonitis.