High Levels of Thyroid Hormone Impair Regulatory T Cell Function Via Reduced PD-1 Expression

Context: Regulatory T cell (Treg) dysfunction plays an important role in the development and progression of Graves' disease (GD). Programmed cell death 1 (PD-1) prompts FoxP3 in Treg expression and enhances the suppressive activity of Tregs. Whether abnormal expression of PD-1 contributes to the breakdown ofTregs and the role of thyroid hormone in the PD-1 expression of Tregs in GD remain substantially undefined. Objective: To evaluate the role of PD-1 in Treg function and triiodothyronine (T3) in PD-1 expression in patients with GD and mice treated with T3. Methods: We recruited 30 patients with GD and 30 healthy donors. PD-1 expression in Tregs and Treg function were determined. To evaluate the effects of thyroid hormone on PD-1 expression in Tregs, we used T3 for the treatment of human peripheral blood mononuclear cells (PBMCs). We then treated mice withT3 to confirm the effect of thyroid hormone on PD-1 expression in Tregs and Tregs function in vivo. Results: PD-1 expression in Tregs and the suppressive function of Tregs significantly decreased in patients with GD. T3 reduced PD-1 expression in human Tregs in a concentration- and time-dependent manner in vitro. High levels of circulatingT3 reduced PD-1 expression in Tregs, impaired Treg function, and disrupted T-helper cell (Th1 and Th2) balance in mice treated with T3. Conclusion: Treg dysfunction in GD patients might be due to downregulation of PD-1 expression in Tregs induced by high levels of serum T3.

Automated summary

The dysfunction of Tregs in GD patients may be caused by the downregulation of PD-1 expression in Tregs induced by high levels of serum T3. T3 reduced PD-1 expression in human Tregs in vitro and impaired Treg function, disrupting the balance of T-helper cells in mice treated with T3.