Expression of IP-10/CXCL10 and MIG/CXCL9 in the Thyroid and Increased Levels of IP-10/CXCL10 in the Serum of Patients with Recent-Onset Graves' Disease

Abstract

Both mRNA and protein expression of the chemokines IP-10/CXCL10 and Mig/CXCL9, as well as of their receptor, CXCR3, were assessed in the thyroid glands of 16 patients suffering from Graves' disease (GD). In addition, IP-10/CXCL10 levels were measured in the serum of 50 GD patients. Expression of IP-10/CXCL10, Mig/CXCL9, and CXCR3 was poor or absent in normal thyroid tissue from patients undergoing thyroidectomy because of primary localized thyroid tumors, while both the chemokines and their receptor were present in most thyroid glands of patients affected by GD. IP-10/CXCL10 and Mig/CXCL9 localized to infiltrating lymphocytes and macrophages, as well as to resident epithelial follicular cells, whereas CXCR3 was mainly found at the level of infiltrating inflammatory cells and endothelial cells from large and small vessels. Of note, maximal expression of IP-10/CXCL10 and Mig/CXCL9 was found in the thyroid gland of patients with recent-onset GD and was correlated with interferon (IFN)-gamma. Accordingly, high levels of IP-10/CXCL10 could be measured in the serum of patients with short-duration GD. Taken together, the results of this study demonstrate that the CXCR3-binding chemokines IP-10/CXCL10 and Mig/CXCL9 play an important role in the recruitment of cells and in the amplification of inflammation in GD. They also suggest that the production of these chemokines by resident follicular epithelial cells may contribute to the recruitment of CXCR3-expressing type 1 T-helper cells in the initial phases of GD.

Changes in expression of T-helper (Th) 1- and Th2-associated chemokine receptors on peripheral blood lymphocytes and plasma concentrations of their ligands, interferon-inducible protein-10 and thymus and activation-regulated chemokine, after antithyroid drug administration in hyperthyroid patients with Graves’ disease

“…Immunohistochemical studies demonstrated high expression of IP-10 in thyroid glands of patients with recent-onset Graves' disease (12,13,17). Thyroid follicular cells as well as infiltrating lymphocytes may be possible sources of IP-10 in sera from patients with newly diagnosed Graves' disease.…”

“…In a cross-sectional study, Romagnani et al immunohistochemically demonstrated high expression of CXCR3 and IP-10 proteins in mononuclear cells surrounding follicular structures in thyroid glands from patients with recent-onset Graves' disease, suggesting the importance of a Th1-dominant response in the initial phase of inflammation in this disease (12). However, no previous reports prospectively identified changes in Th1/Th2 balance according to expression of chemokine receptors and their ligands after the patients began treatment.…”

“…The chemokine receptors CXCR3 and CCR5 are expressed exclusively on Th1 lymphocytes (10), while Th2 lymphocytes preferentially express CCR4 and CCR3 (11). Recently, Romagnani et al demonstrated recruitment of CXCR3-expressing Th1 lymphocytes and expression of the corresponding ligand, interferoninducible protein (IP)-10, in thyroid glands of patients at the initial phase of Graves' disease; this suggested Th1 rather than Th2 dominance within the thyroid gland at the onset of illness (12). Several other studies also reported increased serum IP-10 in patients with autoimmune thyroid diseases including Graves' disease (13)(14)(15).…”

Discrimination between Active and Latent Tuberculosis Based on Ratio of Antigen-Specific to Mitogen-Induced IP-10 Production

“…Therefore, the use of the IP-10 ratio might support an improved diagnosis of active TB disease when combined with the standard diagnostic methods, including microbiology, molecular tests, and clinical and radiological assessments. IP-10 (also known as CXCL10 or IFN-␥-induced protein 10) is a chemokine that is expressed at a high level in inflammatory diseases such as systemic lupus erythematosus, thyroid disease, acute coronary syndrome, and allergies (28)(29)(30). IP-10 is expressed in the bronchial epithelium (31) and in inflamed tissues (32) of active TB patients, who demonstrate upregulation of the helper T (Th) 1-type cytokine IFN-␥.…”

Differential chemokine expression in chronic GVHD of the conjunctiva

“…23,24 It has been demonstrated that members of the chemokine superfamily are involved in immunological and autoimmunological diseases. [25][26][27] The upregulation of several chemokines is associated with acute GVHD. 28,29 However, the pathogenic role of chemokines in chronic conjunctival GVHD remains elusive to a large extent.…”