alpha-Galactosylceramide, a ligand of natural killer T cells, inhibits allergic airway inflammation.
alpha-Galactosylceramide, a ligand of natural killer T cells, inhibits allergic airway inflammation.
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DOI：
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发表时间：
2005
影响因子：
6.4
通讯作者：
H. Matsuda;T. Suda;J. Sato;T. Nagata;Y. Koide;K. Chida;Hirotoshi Nakamura
中科院分区：
文献类型：
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作者：
H. Matsuda;T. Suda;J. Sato;T. Nagata;Y. Koide;K. Chida;Hirotoshi Nakamura
α-半乳糖苷神经酰胺 (α-GalCer) 是自然杀伤 T 细胞 (NKT 细胞) 的特异性配体，通过产生干扰素 (IFN)-gamma 和白细胞介素 (IL)-4 来调节肿瘤排斥和自身免疫等免疫反应。然而，尚未确定 α-GalCer 激活的 NKT 细胞是否调节过敏性炎症。由于 α-GalCer 诱导 NKT 细胞产生大量 IFN-γ，因此我们假设体内施用 α-GalCer 可以抑制小鼠过敏性气道炎症。引人注目的是，单次腹腔注射 α-GalCer 几乎完全消除了肺组织以及支气管肺泡灌洗液中嗜酸性粒细胞的浸润。这种过敏性炎症的抑制与支气管肺泡灌洗液中 IL-4、IL-5 和 IL-13 水平以及杯状细胞数量的显着降低有关。此外，该配体显着抑制吸入乙酰甲胆碱的气道高反应性，并提高卵清蛋白特异性 IgG2a 的血清水平，同时降低卵清蛋白特异性 IgE 的血清水平。然而，在 IFN-γ 敲除小鼠中，α-GalCer 未能在该哮喘模型中发挥这种抑制作用。这些结果表明，α-GalCer 可能通过配体激活的 NKT 细胞产生 IFN-γ 来预防过敏性气道炎症，这表明 α-GalCer 在哮喘中的潜在治疗应用。
alpha-Galactosylceramide (alpha-GalCer) is a specific ligand of natural killer T cells (NKT cells) that regulates the immune responses such as tumor rejection and autoimmunity by producing interferon (IFN)-gamma and interleukin (IL)-4. However, it has not been determined whether alpha-GalCer-activated NKT cells modulate allergic inflammation. Because alpha-GalCer induces a large amount of IFN-gamma production by NKT cells, we hypothesized that an in vivo administration of alpha-GalCer could inhibit allergic airway inflammation in mice. Strikingly, a single intraperitoneal injection of alpha-GalCer almost completely abrogated an infiltrate with eosinophils in the lung tissue as well as in the bronchoalveolar lavage. This inhibition of allergic inflammation was associated with a significant decrease in the levels of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid and in the number of goblet cells. In addition, this ligand significantly inhibited airway hyperresponsiveness to inhaled methacholine and raised the serum levels of ovalbumin-specific IgG2a with a decrease in those of ovalbumin-specific IgE. In IFN-gamma knockout mice, however, alpha-GalCer failed to exert such inhibitory effects in this asthma model. These results indicate that alpha-GalCer prevents allergic airway inflammation possibly through IFN-gamma production by ligand-activated NKT cells, suggesting the potential therapeutic application of alpha-GalCer in asthma.