title: 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.
authors.affiliation: Department of Molecular Diagnostics and Tissue Typing, Osijek University Hospital, Josipa Huttlera 4, 31000 Osijek, Croatia; Faculty of Medicine, University of Osijek, Cara Hadrijana 10E, 31000 Osijek, Croatia; Laboratory of Immunogenomics, Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacký University, 775 20 Olomouc, Czech Republic.
authors.forename: Stana
authors.identifier: 0000-0003-0136-7720
authors.initials: S
authors.lastname: Tokić
authors.affiliation: Faculty of Medicine, University of Osijek, Cara Hadrijana 10E, 31000 Osijek, Croatia; Clinical Institute of Nuclear Medicine and Radiation Protection, Osijek University Hospital, Josipa Huttlera 4, 31000 Osijek, Croatia.
authors.forename: Mario
authors.identifier: 0000-0001-8995-6137
authors.initials: M
authors.lastname: Štefanić
authors.affiliation: Faculty of Medicine, University of Osijek, Cara Hadrijana 10E, 31000 Osijek, Croatia.
authors.forename: Ljubica
authors.identifier: 0000-0001-7497-296X
authors.initials: L
authors.lastname: Glavaš-Obrovac
authors.affiliation: Department of Molecular Diagnostics and Tissue Typing, Osijek University Hospital, Josipa Huttlera 4, 31000 Osijek, Croatia.
authors.forename: Sonja
authors.identifier: 0000-0002-7773-6994
authors.initials: S
authors.lastname: Jaman
authors.affiliation: Laboratory of Immunogenomics, Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacký University, 775 20 Olomouc, Czech Republic.
authors.forename: Eva
authors.identifier: 0000-0002-6813-5150
authors.initials: E
authors.lastname: Novosadová
authors.affiliation: Laboratory of Immunogenomics, Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacký University, 775 20 Olomouc, Czech Republic.
authors.forename: Jana
authors.identifier: 0000-0003-4581-3809
authors.initials: J
authors.lastname: Petrkova
authors.affiliation: Laboratory of Immunogenomics, Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacký University, 775 20 Olomouc, Czech Republic.
authors.forename: Zdenka
authors.identifier: 0000-0002-7983-3333
authors.initials: Z
authors.lastname: Navratilova
authors.affiliation: Department of Molecular Diagnostics and Tissue Typing, Osijek University Hospital, Josipa Huttlera 4, 31000 Osijek, Croatia.
authors.forename: Mirjana
authors.identifier: 0000-0002-5418-3178
authors.initials: M
authors.lastname: Suver Stević
authors.affiliation: Laboratory of Immunogenomics, Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacký University, 775 20 Olomouc, Czech Republic.
authors.forename: Martin
authors.identifier: 0000-0002-4517-7825
authors.initials: M
authors.lastname: Petrek
mesh_terms: D000328:Adult; D001327:Autoimmune Diseases / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D050031:Hashimoto Disease / Q000276:immunology / Q000378:metabolism*; D006728:Hormones / Q000627:therapeutic use; D006801:Humans; D007037:Hypothyroidism / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism*; D015854:Up-Regulation; D000098815:T-bet Transcription Factor
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006728:Hormones; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor