The role of Tregs cells in regulating immunity in IgG4-related diseases

Regulatory T cells (Tregs) play a complex and pivotal role in the pathogenesis of IgG4-related disease (IgG4-RD). Research has demonstrated abundant Treg infiltration within the lesional tissues of patients with IgG4-RD, often accompanied by increased Treg counts in peripheral blood, suggesting a compensatory host response aimed at suppressing aberrant immune activation. However, these Tregs appear to be subject to functional dysregulation or plasticity. On one hand, through the secretion of inhibitory cytokines such as IL-10 and TGF-, Tregs directly facilitate the production of IgG4 antibodies by plasma cells and contribute to tissue fibrosis. On the other hand, their immunosuppressive capacity may be relatively insufficient to effectively curb the hyperactivation of follicular helper T cells (Tfh) and B cells, resulting in the generation of pathogenic autoantibodies and the perpetuation of chronic inflammation. Consequently, Tregs exhibit a "double-edged sword" characteristic in IgG4-RD: they concurrently drive the pathognomonic features of the disease—such as elevated IgG4 levels and fibrosis—while failing to fully uphold immune homeostasis, highlighting the modulation of Treg balance and function as a potential therapeutic avenue. This review aims to elucidate the core mechanisms of Tregs in IgG4-RD and evaluate their clinical potential as biomarkers and therapeutic targets, thereby providing novel insights for the diagnosis and management of this disease.