Analysis of Regulatory T Cell Subsets and Their Expression of Helios and PD-1 in Patients with Hashimoto Thyroiditis.

Yifang Hu,Dai Cui,Lin Jiang,Xuqin Zheng,Huanhuan Chen,Lijuan Zhang,Xiaoyun Liu,He Shi

doi:10.1155/2019/5368473

Yifang Hu, Dai Cui + Show 6 more

Open Access

https://doi.org/10.1155/2019/5368473

Copy DOI

Abstract

Hashimoto thyroiditis (HT) is an autoimmune disease that presumably arises consequent to loss of immune tolerance to autoantigen in thyroid. Regulatory T cells (Tregs) are considered to play a vital role in maintaining the immune balance, as they own intensive suppressive function. This study was undertaken to analyze numbers of Tregs and their expressions of Helios and PD-1 in HT patients. It also aimed to explore the relationship of these with thyroid function and specific autoantibodies. Peripheral blood mononuclear cells (PBMCs) were extracted from blood of 20 healthy controls (HC) and 42 HT patients with varying thyroid functions (10 overt hypothyroidism, 12 subclinical hypothyroidism, and 20 euthyroidism). We performed flow cytometry analysis in PBMCs to detect CD4+CD25+Foxp3+Tregs and their subsets, including CD45RO+Foxp3high activated Treg cells (aTregs), CD45RO−Foxp3low resting Tregs cells (rTregs), and CD45RO+Foxp3low secreting Treg cells (sTregs), as well as the expression of Helios and PD-1 on these cells. The results showed that the percentage of Tregs, aTregs was significantly lower in HT patients and it showed inverse correlation to thyroid function states, in comparison with these in healthy controls. In addition, patients with HT showed decreased expression of Helios in aTregs, while having increased expression of PD-1 in Tregs and sTregs. The levels of Tregs, aTregs, and Helios expressing aTregs were all negatively correlated with antithyroid antibodies. In conclusion, the deficiency of Tregs frequency and aberrant expressions of Helios and PD-1 may possibly contribute to thyroid immune damage in HT.

Highlights

Hashimoto thyroiditis (HT), the most common autoimmune thyroid disease (AITD), is an organ-specific immune disease characterized by immune T cells and antibody-mediated process [1]
Samples derived from 20 healthy controls (HC), 20 eHT, 12 subclinical hypothyroidism (sHT), and 10 overt hypothyroidism (oHT) were included in our study
Our data indicated that HT patients exhibit low percentage of classical Tregs and activated Treg cells (aTregs), and these cells had dynamic changes in the progression of HT

Summary

Introduction

Hashimoto thyroiditis (HT), the most common autoimmune thyroid disease (AITD), is an organ-specific immune disease characterized by immune T cells and antibody-mediated process [1]. Regulatory T cells (Tregs) play a crucial role in maintaining homeostasis by dampening and preventing the excessive inflammatory reactions. Advances in our cognition of Tregs have resulted in the discovery of various subtypes, including mainly IL-10-producing Tr1 (type 1 Treg), TGF-β-producing CD4+ Th3 (T helper 3), and CD4+CD25+ Foxp Tregs. CD4+CD25+Foxp3+ T cells have been a typical and recognized characterization of Tregs up to now. Foxp is a master transcription molecule and functional regulator of Tregs, which plays a crucial role in conferring suppressive function to CD4+CD25+ Tregs by amplifying the expression of Treg cell-type gene such as CD25, IL-10, and CTLA-4 [6].

Methods

Results

Discussion

Conclusion