Th1 chemokines in autoimmune endocrine disorders

CONTEXT: The chemokine receptor (CXCR)3 and its chemokines CXCL10, CXCL9 and CXCL11 are implicated in the pathogenesis of autoimmune diseases. Here, we review these chemokines in "autoimmune thyroiditis" (AT), "Graves' disease" (GD), "thyroid eye disease (TED), "Type 1 diabetes" (T1D), "Addison's disease" (AAD). EVIDENCE ACQUISITION: A PubMed revision of the literature was conducted searching for the above mentioned chemokines in combitation with AT, GD, TED, T1D, AAD. EVIDENCE SYNTHESIS: Thyroid follicular cells in AT and GD, retroorbital cells in TED (fibroblasts, preadipocytes, myoblasts), β cells and islets in T1D, and adrenal cells in AAD, respond to IFN-γ stimulation producing large amounts of these chemokines. Furthermore, lymphocytes and PBMC are in part responsible for the secreted Th1 chemokines. In AT, GD, TED, T1D, AAD circulating levels of these chemokines have been shown to be high. Furthermore these chemokines have been associated with the early phases of the autoimmune response in all the above mentioned disorders. High levels of these chemokines have been associated also with the "active phase" of the disease in GD, and also in TED. Other studies have shown an association with the severity of hypothyroidism in AD, of hyperthyroidism in GD, with severity of TED, or with fulminant T1D. CONCLUSION: The above mentioned data have shown the importance of the Th1 immune response in different endocrine autoimmune diseases, and many studies have suggested that CXCR3, and its chemokines, might be considered potential targets of new drugs for the treatment of these disorders.