Effects of allergen immunotherapy on follicular regulatory T cells

Abstract

Purpose of review Emerging evidence indicating that the dysfunction of T follicular regulatory (TFR) cells contributes to excessive immunoglobulin E (IgE) production and the development of allergic diseases. Conversely, allergen immunotherapy (AIT) modulates TFR cells abundance and function to promote immune tolerance. This review focus on the role of TFR 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 TFR cells in the context of allergic diseases. Recent findings Numerous studies have consistently demonstrated that TFR 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 TFR cells, which exert direct and indirect effects on B cells. In patients with allergic rhinitis, reduced frequencies of circulating or tonsillar TFR cells have been reported, along with impaired functionality in suppressing IgE production. AIT, whether administered subcutaneously or sublingually, reinstates the frequency and functionality of TFR cells in allergic rhinitis patients, accompanied by changes of the chromatin accessibility of TFR cells. The increase in TFR cell frequency following AIT is associated with the amelioration of clinical symptoms. Summary TFR cells exert an inhibitory effect on IgE production and demonstrate a correlation with the clinical efficacy of AIT in patients with allergic rhinitis, suggesting TFR cells hold promise as a therapeutic target for allergic diseases and potential biomarker for AIT.