Burton Oliver T, Noval Rivas Magali, Zhou Joseph S, Logsdon Stephanie L, Darling Alanna R, Koleoglou Kyle J, Roers Axel, Houshyar Hani, Crackower Michael A, Chatila Talal A, Oettgen Hans C
Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Division of Immunology, Boston Children's Hospital, Boston, MA 02115, USA.
Immunity. 2014 Jul 17;41(1):141-51. doi: 10.1016/j.immuni.2014.05.017. Epub 2014 Jul 10.
Immunoglobulin E (IgE) antibodies are known for triggering immediate hypersensitivity reactions such as food anaphylaxis. In this study, we tested whether they might additionally function to amplify nascent antibody and T helper 2 (Th2) cell-mediated responses to ingested proteins and whether blocking IgE would modify sensitization. By using mice harboring a disinhibited form of the IL-4 receptor, we developed an adjuvant-free model of peanut allergy. Mast cells and IgE were required for induction of antibody and Th2-cell-mediated responses to peanut ingestion and they impaired regulatory T (Treg) cell induction. Mast-cell-targeted genetic deletion of the FcεRI signaling kinase Syk or Syk blockade also prevented peanut sensitization. In mice with established allergy, Syk blockade facilitated desensitization and induction of Treg cells, which suppressed allergy when transferred to naive recipients. Our study suggests a key role for IgE in driving Th2 cell and IgE responses while suppressing Treg cells in food allergy.
免疫球蛋白E（IgE）抗体以引发如食物过敏反应等速发型超敏反应而闻名。在本研究中，我们测试了它们是否可能还具有放大新生抗体和辅助性T细胞2（Th2）介导的对摄入蛋白质的反应的功能，以及阻断IgE是否会改变致敏作用。通过使用携带IL-4受体去抑制形式的小鼠，我们建立了一个无佐剂的花生过敏模型。肥大细胞和IgE是诱导对花生摄入的抗体和Th2细胞介导反应所必需的，并且它们会损害调节性T（Treg）细胞的诱导。对肥大细胞靶向性基因敲除FcεRI信号激酶Syk或阻断Syk也可预防花生致敏。在已建立过敏的小鼠中，阻断Syk促进脱敏和Treg细胞的诱导，当将这些Treg细胞转移到未致敏的受体时，它们可抑制过敏反应。我们的研究表明，IgE在食物过敏中驱动Th2细胞和IgE反应同时抑制Treg细胞方面发挥关键作用。
