高甲状腺激素水平通过降低 PD-1 表达来损害调节性 T 细胞功能。

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

机构信息

Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

出版信息

J Clin Endocrinol Metab. 2021 Aug 18;106(9):2738-2753. doi: 10.1210/clinem/dgab191.

DOI:10.1210/clinem/dgab191

PMID:33758937

Abstract

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 of Tregs 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 with T3 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 circulating T3 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.

摘要

背景

调节性 T 细胞（Treg）功能障碍在格雷夫斯病（GD）的发生和发展中起重要作用。程序性细胞死亡 1（PD-1）促使 Treg 中 FoxP3 的表达，并增强 Treg 的抑制活性。PD-1 的异常表达是否导致 Treg 的破坏以及甲状腺激素在 GD 中 Treg 的 PD-1 表达中的作用仍未得到充分定义。

目的

评估 PD-1 在 GD 患者和 T3 治疗的小鼠的 Treg 功能中的作用以及三碘甲状腺原氨酸（T3）在 PD-1 表达中的作用。

方法

我们招募了 30 名 GD 患者和 30 名健康供体。测定 Tregs 中的 PD-1 表达和 Treg 功能。为了评估甲状腺激素对 Tregs 中 PD-1 表达的影响，我们使用 T3 治疗人外周血单核细胞（PBMCs）。然后，我们用 T3 处理小鼠，以确认甲状腺激素对 Tregs 中 PD-1 表达和 Tregs 功能的体内影响。

结果

GD 患者 Tregs 中的 PD-1 表达和 Treg 的抑制功能明显降低。T3 体外以浓度和时间依赖的方式降低人 Tregs 中的 PD-1 表达。循环 T3 水平升高会降低 T3 治疗小鼠 Tregs 中的 PD-1 表达，损害 Treg 功能，并破坏 T 辅助细胞（Th1 和 Th2）平衡。