Emerging evidence indicating that the dysfunction of T follicular regulatory (T FR ) cells contributes to excessive immunoglobulin E (IgE) production and the development of allergic diseases. Conversely, allergen immunotherapy (AIT) modulates T FR cells abundance and function to promote immune tolerance. This review focus on the role of T FR cells in allergic diseases and AIT, with the objective of providing novel insights into the mechanisms underlying immune tolerance of AIT and proposing the potential targeting of T FR cells in the context of allergic diseases.Numerous studies have consistently demonstrated that T FR cells play a pivotal role in the inhibition of class switch recombination to IgE in both humans and specific murine models. This suppression is attributed to the actions of neuritin and IL-10 secreted by T FR cells, which exert direct and indirect effects on B cells. In patients with allergic rhinitis, reduced frequencies of circulating or tonsillar T FR cells have been reported, along with impaired functionality in suppressing IgE production. AIT, whether administered subcutaneously or sublingually, reinstates the frequency and functionality of T FR cells in allergic rhinitis patients, accompanied by changes of the chromatin accessibility of T FR cells. The increase in T FR cell frequency following AIT is associated with the amelioration of clinical symptoms.T FR cells exert an inhibitory effect on IgE production and demonstrate a correlation with the clinical efficacy of AIT in patients with allergic rhinitis, suggesting T FR cells hold promise as a therapeutic target for allergic diseases and potential biomarker for AIT.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.