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Thyrocytes from Autoimmune Thyroid Disorders Produce the Chemokines IP-10 And Mig and Attract CXCR3+ Lymphocytes

Departments of Endocrinology (M.Á.G.-L., M.M.) and Immunology (D.S., F.S.-M.), Hospital de la Princesa, Universidad Autónoma, Madrid 28006, Spain

Address all correspondence and requests for reprints to: Dr. Monica Marazuela, Servicio de Endocrinología, Hospital de la Princesa, Diego de León 62, Madrid 28006, Spain. E-mail: mmarazuela{at}hlpr.insalud.es

Abstract

To better understand the selective migration of lymphocytes in autoimmune thyroid disorders (AITDs), we analyzed thyroid samples and demonstrated an enhanced expression of the chemokines interferon (IFN)-inducible protein (Ip)-10 and regulated on activation normal T lymphocyte expressed and secreted (RANTES) in thyroids from AITD patients. Ip-10 and monokine induced by IFN- (Mig) were expressed in vivo in thyroid follicular cells (TFCs) from AITD thyroids. Interestingly, Ip-10 mRNA, although not basally detected in cultured TFCs, was strongly induced by IFN- and synergistically increased by TNF- addition. Furthermore, high levels of Ip-10 protein were detected in the supernatants of IFN--stimulated TFCs. Likewise, Mig protein was strongly induced in TFCs by the same stimuli as Ip-10. Unlike Ip-10 and Mig, the expression of RANTES was induced mainly by TNF-. In addition, intrathyroidal lymphocytes from AITD patients showed higher expression of CXCR3, CCR2, and CCR5 chemokine receptors than autologous peripheral blood lymphocytes. T lymphoblasts expressing CXCR3 showed an increased migration to supernatants from stimulated TFCs, which was abolished by specific antibodies to the chemokines Ip-10 and Mig, as well as to their receptor CXCR3. Taken together, these data suggest a potential role of TFCs, through the production of the chemokines Ip-10, Mig and RANTES, in regulating the recruitment of specific subsets of activated lymphocytes in AITDs.

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