Department of Immunology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
Nat Immunol. 2010 Jul;11(7):601-7. doi: 10.1038/ni.1886. Epub 2010 Jun 6.
Anaphylaxis is a life-threatening immediate hypersensitivity reaction triggered by antigen capture by immunoglobulin E (IgE) bound to the high-affinity IgE receptor (FcvarepsilonRI) on mast cells. However, the regulatory mechanism of mast cell activation is not completely understood. Here we identify an immunoglobulin-like receptor, Allergin-1, that contains an immunoreceptor tyrosine-based inhibitory motif (ITIM)-like domain, and show it was preferentially expressed on mast cells. Mouse Allergin-1 recruited the tyrosine phosphatases SHP-1 and SHP-2 and the inositol phosphatase SHIP. Coligation of Allergin-1 and FcvarepsilonRI suppressed IgE-mediated degranulation of bone marrow-derived cultured mast cells. Moreover, mice deficient in Allergin-1 developed enhanced passive systemic and cutaneous anaphylaxis. Thus, Allergin-1 suppresses IgE-mediated, mast cell-dependent anaphylaxis in mice.
过敏反应是一种危及生命的即刻超敏反应，由免疫球蛋白 E（IgE）与高亲和力 IgE 受体（FcεRI）结合，从而捕获抗原所触发。然而，肥大细胞激活的调控机制尚未完全阐明。在这里，我们鉴定了一种免疫球蛋白样受体，即 Allergin-1，它包含一个免疫受体酪氨酸抑制基序（ITIM）样结构域，并表明其优先在肥大细胞上表达。小鼠 Allergin-1 募集了酪氨酸磷酸酶 SHP-1 和 SHP-2 以及肌醇磷酸酶 SHIP。Allergin-1 和 FcεRI 的共交联抑制了骨髓源性培养的肥大细胞的 IgE 介导的脱颗粒。此外，缺乏 Allergin-1 的小鼠发展出增强的被动全身性和皮肤过敏反应。因此，Allergin-1 抑制了小鼠的 IgE 介导的、依赖肥大细胞的过敏反应。
