Mechanisms of allergen immunotherapy supporting its disease-modifying effect

Immunotherapy. 2022 Jun;14(8):627-638. doi: 10.2217/imt-2021-0325. Epub 2022 Apr 13.

Abstract

Allergen immunotherapy (AIT) is considered the only disease-modifying treatment available at present for allergic disorders. Its main benefits include improvement of symptoms, decreased need for pharmacotherapy, prevention of new sensitizations and sustained effect after AIT completion. The key pillars of AIT-induced tolerance include a shift from Th2 to Th1 response, an increase of regulatory T and B cells, pro-inflammatory effector cell downregulation and IgE suppression, in addition to IgG4, IgA and IgD induction. AIT may also induce trained immunity, characterized by a durable decrease in group 2 of innate lymphoid cells (ILCs) and increased ILC1 and ILC3s. Understanding the immune mechanisms of AIT is essential for validating biomarkers for the prediction of AIT response and for achieving AIT success.

Keywords: IL-10; allergen immunotherapy; biomarkers; immune tolerance; innate lymphoid cells; regulatory B cells; regulatory T cells; trained immunity.

Plain language summary

In the last decades, allergic diseases have become a public health concern worldwide. Currently, their treatment is mainly based on medications that control the symptoms or decrease future disease risk. The only disease-modifying treatment available for allergic diseases is allergen immunotherapy (AIT). Its main benefits include improvement of symptoms, prevention of new sensitizations and sustained effect after therapy completion. The allergen tolerance induced by AIT is explained by an increase in the number of regulatory immune cells, which reduce inflammation, and a progressive decrease in pro-inflammatory immune cells and IgE synthesis. Better understanding of the mechanisms of AIT is essential for improving efficacy and safety.

Publication types

  • Review

MeSH terms

  • Allergens* / therapeutic use
  • Desensitization, Immunologic
  • Humans
  • Hypersensitivity* / therapy
  • Immune Tolerance
  • Immunity, Innate
  • Lymphocytes

Substances

  • Allergens