Chemokines (chemotactic cytokines) are small proteins (with cytokine activity), that induce directed chemotaxis in nearby responsive cells [1]; some of them have proinflammatory activity, while others are homeostatic. Homeostatic chemokines regulate the process of cell migration in the tissue development or maintenance, whereas pro-inflammatory chemokines recruit the immune system cells in inflammation or infection sites [2]. Chemokines are classified into four main subfamilies: XC, CXC, CX3C and CC. They carry out the biological effects upon their interaction with chemokine receptors, which are transmembrane receptors linked to G protein and located on target cells [2].

The chemokine receptor (CXCR)3 is a member of C-X-C chemokine receptors family and is a seven trans-membrane receptor coupled to G proteins, having two isoforms: CXCR3A and CXCR3B [1]. CXCR3 interacts with interferon (IFN)-gamma-inducible chemokines (or Type-1 helper (Th1) dependent chemokines]: (a) monokine induced by IFN-gamma (MIG)/CXCL9; (b) IFN-gamma-inducible protein 10 (IP-10)/chemokine ligand 10 (CXCL)10; (c) IFN-gamma-inducible T-cell alpha chemoattractant (I-TAC)/CXCL11 [1]. Various cells, including Natural killer cells, activated T lymphocytes; some endothelial and epithelial cells, etc. express this receptor. In particular, Th1 cells, which are attracted in the tissues by the Th1 chemokines released during inflammation, show CXCR3 [3], *[4].

In fact, CXCR3 and its ligands carry out a pivotal role in the engagement of inflammatory cells. Damaged cells secrete CXCL9, CXCL10, and CXCL11 that attract Th1 lymphocytes [5], [6] increasing the release of tumor necrosis factor (TNF)-alpha and IFN-gamma in inflamed tissues. This process stimulates the release of Th1 chemokines by various cells, supporting an amplification feedback loop *[4], [7]. Later, released chemokines move in circulation and it was observed that elevated Th1 chemokines levels in peripheral fluids represent a marker of the host inflammatory response [3], *[4], [7], [8].

Different autoimmune diseases, such as autoimmune thyroiditis (AT) *[9], [10], [11], [12], *[13], [14], [15], Graves’ disease (GD) [16], *[17], Graves’ ophthalmopathy (GO) [18], and type 1 diabetes (T1D) [19], [20] show higher levels of Th1 chemokines. Moreover, increased levels have been shown in systemic rheumatological disorders, including systemic lupus erythematosus [21], rheumatoid arthritis [22], systemic sclerosis [23], psoriatic arthritis [24], sarcoidosis [25], hepatitis C virus (HCV)-related cryoglobulinemia [26], [27], other HCV immunomediated disorders [28], [29] and also in cancers [30].

Here, we review the role of chemokines in thyroid autoimmunity.