IgEb immune complexes activate macrophages through FcγRIV binding
IgEb immune complexes activate macrophages through FcγRIV binding
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DOI：
10.1038/ni1477
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发表时间：
2007-07-01
影响因子：
30.5
通讯作者：
Cooper, Max D.
中科院分区：
文献类型：
--
作者：
Hirano, Masayuki;Davis, Randall S.;Cooper, Max D.
由于Fc受体（FcR）的功能分析严重依赖于小鼠模型，因此另一种Fc γ受体的鉴定特别值得注意。我们证明，Fc γ RIV，在这里确定为灵长类Fc γ RIII的小鼠直系同源物，需要FcR γ链的关联以在骨髓细胞上实现最佳表达和功能;其信号传导潜力也通过能够募集衔接分子Crk-L和磷脂酰肌醇-3-OH激酶的细胞质“YEEP”基序增强。出乎意料的是，Fc γ RIV“优先”结合“B”同种异型的免疫球蛋白E抗体（IgE（B））以及IgG 2 a和IgG 2 B抗体。通过抗原-IgE（B）免疫复合物连接Fc γ RIV可促进巨噬细胞介导的吞噬作用、向T细胞呈递抗原、产生促炎细胞因子和皮肤过敏反应的晚期。因此，IgE（B）抗体介导的巨噬细胞反应修饰可能影响小鼠哮喘模型和寄生虫易感性的品系依赖性差异。
Because functional analysis of Fc receptors (FcRs) relies heavily on mouse models, the identification of another Fc gamma receptor is particularly noteworthy. We demonstrate that Fc gamma RIV, identified here as the mouse ortholog of primate Fc gamma RIII, required association of the FcR gamma-chain for optimal expression and function on myeloid cells; its signaling potential was also enhanced by a cytoplasmic 'YEEP' motif that was able to recruit the adaptor molecule Crk-L and phosphatidylinositol-3-OH kinase. Unexpectedly, Fc gamma RIV 'preferentially' bound immunoglobulin E antibodies of the 'b' allotype (IgE(b)) as well as IgG2a and IgG2b antibodies. Ligation of Fc gamma RIV by antigen-IgE(b) immune complexes promoted macrophage-mediated phagocytosis, presentation of antigen to T cells, production of proinflammatory cytokines and the late phase of cutaneous allergic reactions. IgE(b) antibody-mediated modification of macrophage responses may therefore influence mouse asthma models and strain-dependent differences in parasite susceptibility.