The Expression of T Cell FOXP3 and T-Bet Is Upregulated in Severe but Not Euthyroid Hashimoto's Thyroiditis.

Stana Tokić,Eva Novosadová,Mirjana Suver Stević,Sonja Jaman,Jana Petrkova,Ljubica Glavaš-Obrovac,Mario Štefanić,Martin Petrek,Zdenka Navratilova

doi:10.1155/2016/3687420

Stana Tokić, Eva Novosadová + Show 7 more

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https://doi.org/10.1155/2016/3687420

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Abstract

Hashimoto's thyroiditis (HT) is an organ-specific autoimmune disorder characterized by progressive thyroid failure. Th1 and Treg subset of CD4+ cells have been implicated in the pathogenesis; however, less is known about their respective roles across the spectrum of HT clinical presentations. To shed more light on CD4+ subsets role in HT, we investigated the mRNA expression levels of several Th1/Treg-associated transcription factors (T-bet/ETS1, HIF1α/BLIMP1/FOXP3) in peripheral blood T cells of 10 hypothyroid, untreated HT patients, 10 hypothyroid patients undergoing hormone replacement therapy, 12 euthyroid HT subjects, and 11 healthy controls by the qRT-PCR. Compared to euthyroid HT patients and controls, both hypothyroid (2.34-fold difference versus controls, P < 0.01) and thyroxine-supplemented patients (2.5-fold, P < 0.001) showed an increased FOXP3 mRNA expression in T cells. Similarly, mRNA expression levels of T-bet were upregulated in severely affected but not in euthyroid HT subjects (2.37-fold and 3.2-fold, hypothyroid and thyroxine-supplemented HT patients versus controls, resp., P < 0.01). By contrast, no differences in mRNA expression levels of ETS1, BLIMP1, and HIF1α were observed across the study groups. In summary, severe but not euthyroid HT was associated with robust upregulation of T-bet and FOXP3 mRNA in peripheral T cells, independent of the thyroid hormone status but proportional to disease activity.

Highlights

Hashimoto’s thyroiditis (HT) is the second most widespread endocrine disorder characterized by autoimmune thyroid destruction and subsequently hypothyroidism
T-helpers 1 (Th1) and Treg subset of CD4+ cells have been implicated in the pathogenesis; less is known about their respective roles across the spectrum of HT clinical presentations
To shed more light on CD4+ subsets role in HT, we investigated the mRNA expression levels of several Th1/Treg-associated transcription factors (T-bet/ETS1, HIF1α/BLIMP1/FOXP3) in peripheral blood T cells of 10 hypothyroid, untreated HT patients, 10 hypothyroid patients undergoing hormone replacement therapy, 12 euthyroid HT subjects, and 11 healthy controls by the quantitative real-time polymerase chain reaction (qRT-PCR)

Summary

Introduction

Hashimoto’s thyroiditis (HT) is the second most widespread endocrine disorder characterized by autoimmune thyroid destruction and subsequently hypothyroidism. CD4+CD25+Treg cells has been associated with thyroid inflammation [3,4,5,6,7,8], disease severity [6,7,8], and HT destructiveness [3, 8]. Th1 and Treg cell polarization is driven by lineage-specific master regulators, encompassing transcription factors (TFs) such as T-bet and FOXP3. ETS1 is essential for mounting effective Th1 responses [9, 10] and maintenance of Treg suppressive function by upregulating FOXP3 [11]. To address the role of T cell TFs in HT, we determined Th1 (T-bet, ETS1) and Treg-associated (HIF1α, BLIMP1, and FOXP3) mRNAs in peripheral blood T cells of HT patients. To explore possible differential expression at different clinical endpoints, we performed subanalyses in disease subsets characterized by distinct stage and residual thyroid function

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