Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna 1090, Austria.
J Immunol. 2011 Jul 1;187(1):164-71. doi: 10.4049/jimmunol.1003392. Epub 2011 May 27.
The IgE-mediated and Th2-dependent late-phase reaction remains a mechanistically enigmatic and daunting element of human allergic inflammation. In this study, we uncover the FcεRI on dendritic cells (DCs) as a key in vivo component of this form of allergy. Because rodent, unlike human, DCs lack FcεRI, this mechanism could be revealed only by using a new transgenic mouse model with human-like FcεRI expression on DCs. In the presence of IgE and allergen, FcεRI(+) DCs instructed naive T cells to differentiate into Th2 cells in vitro and boosted allergen-specific Th2 responses and Th2-dependent eosinophilia at the site of allergen exposure in vivo. Thus, FcεRI on DCs drives the cascade of pathogenic reactions linking the initial allergen capture by IgE with subsequent Th2-dominated T cell responses and the development of late-phase allergic tissue inflammation.
IgE 介导和 Th2 依赖性晚期反应仍然是人类过敏炎症中一种机制上神秘且令人畏惧的元素。在这项研究中，我们揭示了树突状细胞（DC）上的 FcεRI 是这种形式过敏的关键体内组成部分。由于啮齿动物不像人类那样缺乏 FcεRI，因此只有通过使用一种新型的转基因小鼠模型，该模型在 DC 上表达类似于人类的 FcεRI，才能揭示这种机制。在 IgE 和过敏原存在的情况下，FcεRI(+) DC 指导幼稚 T 细胞在体外分化为 Th2 细胞，并在体内过敏原暴露部位增强过敏原特异性 Th2 反应和 Th2 依赖性嗜酸性粒细胞增多。因此，DC 上的 FcεRI 驱动了将初始过敏原捕获与随后的 Th2 主导 T 细胞反应以及晚期过敏组织炎症发展联系起来的致病反应级联。
