Interrupting reactivation of immunologic memory diverts the allergic response and prevents anaphylaxis.
J Allergy Clin Immunol
; 147(4): 1381-1392, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33338539
ABSTRACT
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Imunoglobulina E
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Receptores de Interleucina-4
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Hipersensibilidade a Amendoim
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Anafilaxia
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Memória Imunológica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article