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

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.

Imbalances in T Cell-Related Transcription Factors Among Patients with Hashimoto’s Thyroiditis

“…26 However, another study demonstrated FOXP3 upregulation in the T cells of peripheral blood samples from patients with HT. 21 This discrepancy is perhaps attributable to differing inclusion criteria used in these studies. 21,35,36 In the current study, expression of the T-bet/ FOXP3, GATA 3 /FOXP3 and RORα/FOXP3 ratios was significantly increased among patients with HT in comparison with the healthy control group; however, while the expression of T-bet, GATA 3 and RORα alone was increased, FOXP3 expression alone was reduced among HT patients.…”

“…21 This discrepancy is perhaps attributable to differing inclusion criteria used in these studies. 21,35,36 In the current study, expression of the T-bet/ FOXP3, GATA 3 /FOXP3 and RORα/FOXP3 ratios was significantly increased among patients with HT in comparison with the healthy control group; however, while the expression of T-bet, GATA 3 and RORα alone was increased, FOXP3 expression alone was reduced among HT patients. Therefore, it is logical that expression of the T-bet/FOXP3, GATA 3 /FOXP3 and RORα/FOXP3 ratios was significantly increased among the HT patients.…”

“…Recently, increased expression of FOXP3 and T-bet was demonstrated among HT patients who were severely affected but not euthyroid. 21 Thus, it seems that different immunopathological mechanisms may be involved in the various expressions of the spectrum of HT-associated diseases. Moreover, thyroid function may also influence the expression of T cell-related transcription factors in HT patients.…”

“…Moreover, thyroid function may also influence the expression of T cell-related transcription factors in HT patients. 21 …”

“…19,20 Although a few studies have investigated transcription factors among HT patients, few have measured Th1/Th2, Th1/Treg, Th2/Treg and Th17/ Treg cell balances at the level of these transcription factors. 21,22 This study therefore aimed to determine the balance of effector T cells-specifically, Th1, Th2, Th17 and Treg cells-at the level of transcription factors by measuring the expression of their master transcription factors-T-bet, GATA 3 , RORα/RORγt and FOXP3, respectively-and determining their ratios in the peripheral blood mononuclear cells (PBMCs) of HT patients in comparison to healthy individuals.…”