IgE-mediated activation of NK cells through FcγRIII

IgE-mediated activation of NK cells through FcγRIII
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DOI:
10.4049/jimmunol.170.6.3054
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发表时间:
2003-03-15
影响因子:
4.4
通讯作者:
Saito, T
Saito, T
中科院分区:
医学2区
文献类型:
--
作者:
Arase, N;Arase, H;Saito, T

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NK细胞表达FcGammaRIII(CD16),参与了免疫球蛋白依赖性细胞的细胞毒作用以及多种细胞因子和趋化因子的产生。NK细胞上的FcGammaRIII由FcGammaRIIIpha和FcRGamma链组成,而肥大细胞上的FcGammaRIII链不同于NK细胞,由FcGammaRIIIpha、FcRIIIpha和FcRGamma组成。肥大细胞显示脱颗粒并释放多种介质,当FcGammaRIII和FcepsilonRI与聚集的IgE交联时,这些介质会引起过敏反应。在本文中,我们检测了IgE是否通过细胞表面FcGammaRIII激活NK细胞。我们发现NK细胞产生几种细胞因子和趋化因子,这些细胞因子和趋化因子与IgE刺激引起的过敏反应有关。此外,NK细胞以FcGammaRIII依赖的方式对IgE包被的靶细胞显示出细胞毒作用。在缺乏FcGammaRIII表达的FcRGamma基因缺陷小鼠的NK细胞中,没有观察到IgE通过FcGammaRIII产生的这些效应。综上所述,这些结果表明,NK细胞可以被IgE通过FcGammaRIII激活,并表现出细胞因子/趋化因子的产生和抗体依赖的细胞毒作用。这些数据表明,不仅肥大细胞,而且NK细胞可能在IgE介导的过敏反应中起作用。
NK cells express FcgammaRIII (CD16), which is responsible for IgG-dependent cell cytotoxicity and for production of several cytokines and chemokines. Whereas FcgammaRIII on NK cells is composed of both FcgammaRIIIalpha and FcRgamma chains, that on mast cells is distinct from NK cells and made of FcgammaRIIIalpha, FcRbeta, and FcRgamma. Mast cells show degranulation and release several mediators, which cause anaphylactic responses upon cross-linking of FcgammaRIII as well as FcepsilonRI with aggregated IgE. In this paper, we examined whether IgE activates NK cells through FcgammaRIII on their cell surface. We found that NK cells produce several cytokines and chemokines related to an allergic reaction upon IgE stimulation. Furthermore, NK cells exhibited cytotoxicity against IgE-coated target cells in an FcgammaRIII-dependent manner. These effects of IgE through FcgammaRIII were not observed in NK cells from FcRgamma-deficient mice lacking FcgammaRIII expression. Collectively, these results demonstrate that NK cells can be activated with IgE through FcgammaRIII and exhibit both cytokine/chemokine production and Ab-dependent cell cytotoxicity. These data imply that not only mast cells but also NK cells may contribute to IgE-mediated allergic responses.