Interrupting reactivation of immunologic memory diverts the allergic response and prevents anaphylaxis
Interrupting reactivation of immunologic memory diverts the allergic response and prevents anaphylaxis
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DOI：
10.1016/j.jaci.2020.11.042
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发表时间：
2021-04-05
影响因子：
14.2
通讯作者：
Jordana, Manel
中科院分区：
文献类型：
--
作者：
Bruton, Kelly;Spill, Paul;Jordana, Manel
背景：针对无害食物抗原的 IgE 产生可能导致过敏反应，这是过敏反应的一种严重危及生命的后果。 IgE 免疫的维持主要由 IgG(+) 记忆 B 细胞促进，因为 IgE(+) 记忆 B 细胞和 IgE(+) 浆细胞分别极其稀缺和短命。 目的：我们的目的是研究花生过敏中 IgE 回忆反应的关键要求。方法：我们使用新型人类 PBMC 培养平台、花生过敏小鼠模型和各种实验读数来评估存在和不存在 IL-4R α 阻断的情况下的 IgE 回忆反应。结果：在人类 PBMC 中，我们证明，在人类 PBMC 中，IL-4/IL-13 信号传导的阻断会在回忆反应激活后中止 IgE 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，T(H)2A 细胞在花生刺激下扩增，尽管 IL-4R α 阻断，但仍保持其致病表型。在过敏小鼠中，除了抗体治疗外，抗 IL-4R α 还可以长期抑制 IgE 回忆反应，并完全防止过敏反应。 结论：本文报告的研究结果增进了我们对食物过敏中介导 IgE 再生的事件的理解。
Background: 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 shortlived, respectively.Objective: Our aim was to investigate the critical requirements for an IgE recall response in peanut allergy. Methods: 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-4R alpha blockade.Results: 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. T(H)2A cells, identified by single-cell RNA sequencing, expanded with peanut stimulation and maintained their pathogenic phenotype in spite of IL-4R alpha blockade. In mice with allergy, anti-IL-4R alpha provided long-lasting suppression of the IgE recall response beyond antibody treatment and fully protected against anaphylaxis.Conclusion: The findings reported here advance our understanding of events mediating the regeneration of IgE in food allergy.