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Interrupting reactivation of immunologic memory diverts the allergic response and prevents anaphylaxis

Published:December 15, 2020DOI:https://doi.org/10.1016/j.jaci.2020.11.042

      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 short-lived, 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-4Rα 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. TH2A 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.

      Conclusion

      The findings reported here advance our understanding of events mediating the regeneration of IgE in food allergy.

      Key words

      Abbreviations used:

      C2 (Cluster 2), CPE (Crude peanut extract), FACS (Fluorescence-activated cell sorting), GFP (Green fluorescent protein), hCD2 (Human CD2), IC (Isotype control), MBC (Memory B cell), MIP (Macrophage inflammatory protein), NK (Natural killer), NKT (Natural killer T), OVA (Ovalbumin), PC (Plasma cell), PE (Phycoerythrin), scRNA-seq (Single-cell RNA sequencing), TFH (Follicular helper T)
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