Elevated Expression and Activation of GPR15 in Immune Cells in Graves’ Disease

GPR15 plays an important role in lymphocyte homing and is a key immune molecule to maintain organ immune homeostasis. Yet, no study on the association between GPR15 and Graves’ disease (GD) is available. In this study, we systematically investigated the expression of GPR15 in different types of immune cells and different tissues of GD patients. We found that the expressions of GPR15 and GPR15L in peripheral blood of GD patients were increased compared with those in healthy controls. A flow cytometry analysis showed that GPR15 positive cells were mainly CD14+ monocytes and CD56+ natural killer cells (NK cells) of innate immunity, T helper cells and cytotoxic T cells of adaptive immunity. We also found that the expressions of GPR15 and GPR15L in the PBMC of GD patients were positively correlated with the Tfh-specific cytokines IL21 and IL4. In addition, immunohistochemistry showed that the level of GPR15 in thyroid tissue of GD patients was higher than that of the control group. Our results demonstrate for the first time that GPR15 is highly expressed in various immune cells in GD patients, suggesting that GPR15-GPR15L is associated with the activation and infiltration of proinflammatory immune cells in the thyroid tissue of GD patients.