Immunological Responses and Biomarkers for Allergen-Specific Immunotherapy Against Inhaled Allergens

Long-term efficacy that occurs with allergen immunotherapy of proven value is associated with decreases in IgE-dependent activation of mast cells and tissue eosinophilia. This suppression of type 2 immunity is accompanied by early induction of regulatory T cells, immune deviation in favor of TH1 responses, and induction of local and systemic IgG, IgG4, and IgA antibodies. These protective antibodies can inhibit allergen-IgE complex formation and consequent mast cell triggering and IgE-facilitated TH2-cell activation. Recent studies have highlighted the importance of innate responses mediated by type 2 dendritic cells and innate lymphoid cells in allergic inflammation. These cell types are under the regulation of cytokines such as thymic stromal lymphopoietin and IL-33 derived from the respiratory epithelium. Novel subsets of regulatory cells induced by immunotherapy include IL-35eproducing regulatory T cells, regulatory B cells, a subset of T follicular regulatory cells, and IL10eproducing group 2 innate lymphoid cells. These mechanisms point to biomarkers that require testing for their ability to predict clinical response to immunotherapy and to inform novel approaches for better efficacy, safety, and longterm tolerance. (C) 2021 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology

Automated summary

Allergen immunotherapy leads to decreased IgE-dependent activation of mast cells and tissue eosinophilia, along with changes in regulatory T cells and cytokines, resulting in reduced allergic inflammation. Research also indicates the importance of innate responses and new subsets of regulatory cells induced by immunotherapy in predicting clinical response and developing novel approaches for better efficacy and long-term tolerance.