2e,f). As an organ-specific autoimmune disease, lymphoid infiltration is a significant feature of HT. To determine whether leptin, IL-17 and RORγt mRNA expression were also expressed in local thyroid tissue, we detected significantly up-regulated levels of leptin, IL-17 and RORγt transcripts in the thyroid tissue EPZ015666 price of six HT patients by PCR analysis (Fig. 3). To investigate a potential role of leptin in the development of Th17 cells in vitro, we treated CD4+ T cells from

HT patients with neutralizing leptin monoclonal antibody in the presence of anti-CD3 and anti-CD28 mAb. As shown in Fig. 4, we detected a substantially decreased frequency of CD4+ Th17 cells and RORγt mRNA expression among naive CD4+ T cells cultured in the presence of anti-leptin mAb. Accumulating data indicate that leptin acts as a proinflammatory cytokine in autoimmune disease animal model, such as EAE [17], non-obese diabetic (NOD) mice [18]and experimental arthritis [19]. In human autoimmune thyroid diseases, the role of leptin seems to be more complicated. It has Pexidartinib molecular weight been reported

that high levels of plasma leptin in women developed postpartum thyroiditis, suggesting a relationship between leptin and postpartum thyroid disease [16]. However, Sieminska and colleagues showed that concentrations of leptin were not altered in postmenopausal women with Hashimoto’s thyroiditis [20]. The differences between these reported findings may be due to patient age and different disease stages. In the present study, our group showed a modest increased level of plasma leptin in HT patients compared to healthy controls, with a positive correlation between plasma leptin and BMI. Previous studies report that activated T lymphocytes could synthesize and produce leptin as an autocrine/paracrine cytokine [14, 21, 22]. Interestingly, the data presented here provide evidence that CD4+ T cell-derived leptin is increased in HT patients. Our results are consistent with a previous study on Dichloromethane dehalogenase MS patients showing

that activated T cells from relapsing–remitting MS patients secreted consistent amounts of leptin in the culture medium [15]. Extensive investigations have elucidated an important role of the T cell-mediated autoimmune response in enhancing autoimmune thyroid disease. A large amount of intrathyroidal lymphocytes in patients are CD4+ T cells, which have been proposed to be involved in the pathogenesis of HT diseases. The previous report showed that Th1/Th2 skew led to inflammatory factor and infiltrated Th1 cells destroy the thyroid gland in HT patients [1]. However, increasing evidence supports that the Th17 cell (IL-23/IL-17) pathway, rather than the Th1 cell [IL-12/interferon (IFN)-γ) pathway, is critical for the development of autoimmune inflammatory diseases [23, 24].