engleski

Expression of IL-23/Th17 pathway mRNA in peripheral T-lymphocytes of patients with Hashimoto's thyroiditis

Hashimoto’s thyroiditis (HT) is an autoimmune thyroid disorder mediated by deregulated T-helper (Th)1 cell responses. Recently, interleukin (IL)-23 driven Th17 cells have been also implicated in disease pathogenesis, but their exact role in thyroid inflammation, disease chronicity and HT destructiveness remains poorly understood. In this study, we analyzed the expression levels of Th17 cell-associated STAT3, IL23 receptor (IL23R), IL21 and IL17A mRNA by quantitative real-time PCR (DDCT method, normalizing to RPL13A) in peripheral T-lymphocytes of 32 HT patients and 16 healthy controls. HT was graded as severe (hypothyroid, requiring hormone replacement therapy) or mild (euthyroid). No difference in age, serum thyrotropin and free thyroxine (T4) levels was found between controls, patients with mild (n = 13) and L-T4 treated, severe HT (n = 19). The expression levels of STAT3, IL17A, IL21 and IL23R mRNA were tightly interrelated (P<0.001 - 0.015, rank correlation), but did not correlate with age, antibodies or serum thyroid hormone levels. The IL17A (P = 0.025, Kruskall-Wallis test) and STAT3 (P = 0.002) gene expression differed by case-control status and need for hormone replacement therapy. On robust, multivariate selection, STAT3 and IL17A mRNA were significantly, incrementally overexpressed in both mildly (PSTAT3 = 0.013, PIL17A = 0.034) and severely affected HT patients (PSTAT3 = 0.0009, PIL17A = 0.011), and correlated with IL21 and IL23R mRNA, respectively. IL21 gene expression was independently related to IL23R and STAT3 mRNA levels. In conclusion, STAT3/IL17A mRNA expression is increased in peripheral T-cells of HT patients and associated with disease severity independently of thyroid hormone availability. Further analysis by combining FACS and protein expression data is needed.

T-helper 17; lymphocyte; Interleukin-23; interleukin-17A; stat-3; interleukin-21; gene expression; mRNA; Hashimoto's thyroiditis

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