Background: IgA is the most abundant immunoglobulin at the mucosal surface and although its role in regulating mucosal immunity is not fully understood, its presence is associated with protection from developing allergic disease.
Objective: We sought to determine the role of IgA immune complexes for therapeutic application to mucosal allergic responses.
Methods: Trinitrophenol (TNP)-specific IgA immune complexes were applied, using TNP-coupled ovalbumin (OVA), to airway and gut mucosal surfaces in systemically sensitized allergic animals to regulate allergen challenge responses. Animals were assessed for both pathologic and immune-mediated responses in the lung and gut, respectively, using established mouse models.
Results: The mucosal application of IgA immune complexes in the lung and gut with TNP-OVA regulated TH2-driven allergic response in the lung and gut, reducing TH2 cytokines and mucus (lung) as well as diarrhea and temperature loss (gut), but increasing IL-10 and the number of regulatory T cells. The IgA-OVA immune complex did not alter peanut-induced anaphylaxis, indicating antigen specificity. Using OVA-specific DO.11-green fluorescent protein IL-4 reporter mouse-derived TH2-skewed cells in a transfer model demonstrated that mucosal IgA immune complex treatment reduced TH2-cell expansion and increased the number of regulatory T cells. To address a potential mechanism of action, TGF-β and IL-10 were induced in bone marrow-derived dendritic cells when they were exposed to IgA immune complex, suggesting a regulatory phenotype induced in dendritic cells that also led to an altered primary T-cell-mediated response in in vitro OVA-specific assays.
Conclusions: These studies highlight one possible mechanism of how allergen-specific IgA may provide a regulatory signal to reduce the development of allergic responses in the lung and gut.
Keywords: IgA; Treg cell; anaphylaxis; asthma; mucosal immunity.
Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.