Exp Clin Endocrinol Diabetes 2019; 127(05): 281-288
DOI: 10.1055/a-0597-8948
Article
© Georg Thieme Verlag KG Stuttgart · New York

Expression of TIGIT and FCRL3 is Altered in T Cells from Patients with Distinct Patterns of Chronic Autoimmune Thyroiditis

Mario Štefanić*
1   Department of Nuclear Medicine and Oncology, Faculty of Medicine, University of Osijek, Osijek, Croatia
,
Stana Tokić*
2   Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Osijek, Osijek, Croatia
3   Department of Laboratory Diagnostics and Clinical Transfusion Medicine, Clinical Institute of Transfusion Medicine, Osijek University Hospital, Osijek, Croatia
,
Mirjana Suver-Stević
3   Department of Laboratory Diagnostics and Clinical Transfusion Medicine, Clinical Institute of Transfusion Medicine, Osijek University Hospital, Osijek, Croatia
,
Ljubica Glavaš-Obrovac
2   Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Osijek, Osijek, Croatia
› Author Affiliations
Further Information

Publication History

received 15 November 2017
revised 21 March 2018

accepted 25 March 2018

Publication Date:
11 June 2018 (online)

Abstract

Background Co-inhibitory receptors (IR), such as TIGIT and FCRL3, provide a checkpoint against highly destructive immune responses. Co-expression of TIGIT and FCRL3, in particular, has been linked to the HELIOS+ subset of regulatory CD4+FOXP3+T-cells. Of these, CD4+FOXP3-exon(E)2+ cells have higher expression of IR and exhibit strongest suppressive properties. Nevertheless, how the expression of TIGIT, FCRL3, HELIOS, and FOXP3E2 is regulated in chronic autoimmune thyroiditis (AT), is not known.

Methods Thirty patients with AT [encompassing spontaneously euthyroid (euAT), hypothyroid-untreated and L-thyroxine-treated cases)] and 10 healthy controls (HC) were recruited. FCRL3, TIGIT, HELIOS and FOXP3E2 mRNA expression levels in peripheral blood (PB) T cells were measured via quantitative real-time PCR and compared to clinicopathological factors.

Results The TIGIT and FCRL3 expression levels from T cells of AT cases were inversely related to the thyroid volume, and were significantly increased in hypothyroid patients (on+off L-thyroxine), but not euAT cases. The FCRL3 expression in PB T cells positively correlated with thyroid-peroxidase autoantibody levels; by contrast, T cells from aged AT patients and combined samples (AT+HC) accumulated more TIGIT mRNA. The patients with higher TIGIT mRNA levels had a greater prevalence of hypothyroidism, showing higher peak thyrotropin levels at diagnosis or at follow-up.

Conclusions Multiple IR, namely FCRL3 and TIGIT, but not the transcription factors HELIOS and FOXP3E2, showed increased mRNA levels in PB T cells from end-stage, long-standing and/or more aggressive AT, in proportion to disease severity. A relation with major clinical subphenotypes was observed, thereby identifying IR as potentially important players in AT.

* Equally contributed authorship


 
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