Department of Immunology, Genentech, Incorporated, South San Francisco, California 94080, USA.
J Biol Chem. 2011 Sep 23;286(38):32891-7. doi: 10.1074/jbc.R110.205104. Epub 2011 Jul 28.
Elevated IgE levels and increased IgE sensitization to allergens are central features of allergic asthma. IgE binds to the high-affinity Fcε receptor I (FcεRI) on mast cells, basophils, and dendritic cells and mediates the activation of these cells upon antigen-induced cross-linking of IgE-bound FcεRI. FcεRI activation proceeds through a network of signaling molecules and adaptor proteins and is negatively regulated by a number of cell surface and intracellular proteins. Therapeutic neutralization of serum IgE in moderate-to-severe allergic asthmatics reduces the frequency of asthma exacerbations through a reduction in cell surface FcεRI expression that results in decreased FcεRI activation, leading to improved asthma control. Our increasing understanding of IgE receptor signaling may lead to the development of novel therapeutics for the treatment of asthma.
血清 IgE 水平升高和对过敏原的 IgE 敏感性增加是过敏性哮喘的主要特征。IgE 与肥大细胞、嗜碱性粒细胞和树突状细胞上的高亲和力 Fcε受体 I（FcεRI）结合，并介导这些细胞在抗原诱导的 IgE 结合的 FcεRI 交联时的激活。FcεRI 的激活通过一系列信号分子和衔接蛋白进行，并受许多细胞表面和细胞内蛋白的负调控。在中重度过敏性哮喘患者中，通过降低细胞表面 FcεRI 表达来中和血清 IgE，从而减少 FcεRI 激活，进而改善哮喘控制，从而减少哮喘恶化的频率。我们对 IgE 受体信号转导的认识不断加深，可能会为哮喘的治疗开发出新的治疗方法。
