Significance of pathological changes and chemokine expression in various organs in a Graves' disease animal model.

Graves’ disease (GD) is the most common autoimmune disease characterized by the loss of immune tolerance induced by the activation of target antigens by the thyrotropin receptor (TSHR) autoantibody. Chemokines may be involved in the autoimmune inflammatory response in GD. In this study, we investigated the mechanism of chemokine expression in different tissues of GD hyperthyroid mice. Adenoviruses encoding the TSHR A subunit were employed to immunize female BALB/c mice to induce GD. HE-stained sections were used to observe the histopathological morphology, and RT-qPCR and immunohistochemistry were used to detect the expression levels of CCL2, CCL5 and ACKR1 in the tissues. ELISA was used to measure the levels of CCL2 and CCL5 in the serum of patients with GD. In HE-stained sections from hyperthyroid mice, the spleen showed hyperplasia of the red medulla, atrophy of the white medulla, hyperplasia of the trabecular veins, hyperplasia of the medullary region of the thymus, steatosis of the hepatocytes, atrophy of cardiomyocytes, atrophy of the kidneys, and necrosis of the adrenal glands and skeletal muscles. CCL5, CCL2 and ACKR1 expression levels were elevated in the spleen of GD hyperthyroid mice; CCL5 and CCL2 expression levels were elevated in thymus tissue; CCL2 and ACKR1 expression levels were elevated in thyroid tissue; and CCL5 expression was decreased in thyroid tissue. Chemokines were differentially expressed in other tissues. The pathological changes in various organs of GD hyperthyroid mice may provide a theoretical basis for studying the pathogenesis of GD complicating extrathyroidal diseases. Chemokines may play crucial roles in the immune mechanisms of GD and extrathyroidal diseases.