McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Peter Munk Cardiac Centre, Toronto, Ontario, Canada.
J Allergy Clin Immunol. 2021 Apr;147(4):1381-1392. doi: 10.1016/j.jaci.2020.11.042. Epub 2020 Dec 15.
IgE production against innocuous food antigens can result in anaphylaxis, a severe life-threatening consequence of allergic reactions. The maintenance of IgE immunity is primarily facilitated by IgG memory B cells, as IgE memory B cells and IgE plasma cells are extremely scarce and short-lived, respectively.
Our aim was to investigate the critical requirements for an IgE recall response in peanut allergy.
We used a novel human PBMC culture platform, a mouse model of peanut allergy, and various experimental readouts to assess the IgE recall response in the presence and absence of IL-4Rα blockade.
In human PBMCs, we have demonstrated that blockade of IL-4/IL-13 signaling aborted IgE production after activation of a recall response and skewed the cytokine response away from a dominant type 2 signature. T2A cells, identified by single-cell RNA sequencing, expanded with peanut stimulation and maintained their pathogenic phenotype in spite of IL-4Rα blockade. In mice with allergy, anti-IL-4Rα provided long-lasting suppression of the IgE recall response beyond antibody treatment and fully protected against anaphylaxis.
The findings reported here advance our understanding of events mediating the regeneration of IgE in food allergy.
针对无害食物抗原的 IgE 产生可导致过敏反应的严重危及生命的后果，即过敏反应。IgE 免疫的维持主要由 IgG 记忆 B 细胞介导，因为 IgE 记忆 B 细胞和 IgE 浆细胞分别非常稀少且寿命短。
我们旨在研究花生过敏中 IgE 回忆反应的关键要求。
我们使用了一种新型人 PBMC 培养平台、一种花生过敏的小鼠模型和各种实验检测方法，在存在和不存在 IL-4Rα 阻断的情况下评估 IgE 回忆反应。
在人 PBMC 中，我们已经证明阻断 IL-4/IL-13 信号转导可在激活回忆反应后阻止 IgE 的产生，并使细胞因子反应偏离主导的 2 型特征。通过单细胞 RNA 测序鉴定的 T2A 细胞在花生刺激下扩增，并尽管存在 IL-4Rα 阻断仍保持其致病性表型。在过敏小鼠中，抗 IL-4Rα 可提供对 IgE 回忆反应的持久抑制作用，超过抗体治疗，并完全预防过敏反应。
这里报告的发现增进了我们对食物过敏中 IgE 再生的介导事件的理解。
