Chemokines and Autoimmune Thyroid Diseases

Abstract

Chemokines are a family of small, structurally related molecules that regulate cell trafficking of various types of leukocytes through interactions with their seven-transmembrane, G protein-coupled receptors. Their major function is the recruitment of leukocytes to inflammation sites, but they also play roles in tumor growth, angiogenesis, organ sclerosis, and autoimmunity. A variety of evidence has accumulated to support the concept that thyroid follicular cells as well as intrathyroidal lymphocytes are able to produce CC and CXC chemokines, which, in turn, promote the initiation and maintenance of an inflammatory process resulting in autoimmune thyroid diseases (AITD). Overexpression of several chemokines in AITD has been demonstrated. Moreover, alterations of CCL2, CCL5, CXCL9, and CXCL10 have been shown in circulation of many patients with AITD. In subjects with Graves' disease, antithyroid drug treatment, radioactive iodine ablation, and thyroidectomy can significantly reduce CXCL10 levels. The measurement of chemokines in serum of AITD patients might provide a useful parameter for the evaluation and prediction of disease activity and progression. Further experimental and clinical studies will expand our understanding of the clinical implications of chemokine detection and the effects of chemokines on the pathogenesis of AITD.

Low levels of circulating platelet factor 4 (PF4, CXCL4) in subclinically hypothyroid autoimmune thyroiditis

“…Their serum levels vary during the course of AIT because of the causes like disease duration and activity, thyroid function status and pharmacological treatment [16]. Though past research focused on the expression of several chemokines in thyroids of patients with AIT, possible role of chemokines has been less extensively studied in sera of patients [5,17]. In 2004, Antonelli et al [18] reported that circulating CXCL10 was increased in patients with AIT and is associated with chronic autoimmune thyroiditis and hypothyroidism and may be regarded as a marker of a more aggressive thyroiditis leading to thyroid destruction.…”

Immunopathogenesis of Thyroid Eye Disease: Emerging Paradigms

“…Overall, the clinical manifestations of glandular GD are predictable and can be treated with relative ease in the vast majority of patients 86. A detailed description of the endocrine derangements associated with GD is beyond the scope of this article, and can be found elsewhere 47,77,105…”

Serum CXCL10 levels and neuromuscular manifestations in patients with autoimmune thyroid diseases

“…In a typical scenario, after IFN-g stimulation, several endocrine cells secrete CXCL10, which in turn recruits Th1 lymphocytes that express CXCR-3 and secrete IFN-g, establishing an important loop for the sustainment of inflammatory reactions [1]. Accordingly, the CXCR-3-binding chemokines have also been proven to play pivotal pathogenic roles in both human studies and mouse models for autoimmune thyroid diseases (AITD) [3].…”