Expression of TIGIT and FCRL3 is Altered in T Cells from Patients with Distinct Patterns of Chronic Autoimmune Thyroiditis
Autor: | Ljubica Glavaš-Obrovac, Mario Štefanić, Stana Tokić, Mirjana Suver-Stević |
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Rok vydání: | 2018 |
Předmět: |
Adult
Male 0301 basic medicine T-Lymphocytes Endocrinology Diabetes and Metabolism Gene Expression Thyrotropin 030209 endocrinology & metabolism Severity of Illness Index Thyroiditis Autoimmune thyroiditis Ikaros Transcription Factor 03 medical and health sciences 0302 clinical medicine Endocrinology Immune system TIGIT Internal Medicine medicine Humans Euthyroid RNA Messenger Receptors Immunologic Aged T-lymphocytes gene expression Hashimoto disease costimulatory and inhibitory T-cell receptors disease attributes thyroid gland business.industry Thyroid Age Factors Thyroiditis Autoimmune Autoantibody FOXP3 Forkhead Transcription Factors General Medicine Middle Aged medicine.disease 030104 developmental biology medicine.anatomical_structure Immunology Female business |
Zdroj: | Experimental and Clinical Endocrinology & Diabetes. 127:281-288 |
ISSN: | 1439-3646 0947-7349 |
Popis: | 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. |
Databáze: | OpenAIRE |
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