Increased Thyroid DPP4 Expression Is Associated With Inflammatory Process in Patients With Hashimoto Thyroiditis

Abstract

Background Dipeptidyl peptidase 4 (DPP4) is originally described as a surface protein in lymphocytes. Lymphocytes infiltration and subsequent destruction of thyroid tissue have been considered as the central pathological mechanism in Hashimoto’s thyroiditis (HT). The present study aimed to investigate the DPP4 expression in peripheral blood and thyroid tissue in HT patients, and explore the role of DPP4 in the pathophysiological process of HT. Methods This case-control study recruited 40 drug-naïve HT patients and 81 controls. The peripheral blood and thyroid specimens were collected for assessing the expression and activity of DPP4. Moreover, scRNA-seq analysis of 6 “para-tumor tissues” samples from scRNA-seq dataset GSE184362 and in-vitro cell experiments were also conducted. Results The HT patients had similar serum concentration and activity of DPP4 with the controls. However, the expression and activity of DPP4 was significantly increased in the thyroid of the HT group than in the control group. The scRNA-seq analysis showed that DPP4 expression was significantly increased in the HT group, and mainly expressed in T cells. Further in vitro studies showed that inhibition of lymphocyte DPP4 activity with sitagliptin downregulated the production of inflammatory factors in co-cultured thyroid cells. Conclusions The DPP4 expression was significantly increased in the thyroid of the HT group than in the control group, and mainly localized in the lymphocytes. Inhibition of lymphocyte DPP4 activity reduced the production of inflammatory factors in co-cultured thyroid cells. Therefore, inhibition of DPP4 may have a beneficial effect by alleviating inflammatory reactions in HT patients.