Thyrocytes from autoimmune thyroid disorders produce the chemokines IP-10 and Mig and attract CXCR3+lymphocytes

To better understand the selective migration of lymphocytes in autoimmune t hyroid disorders (AITDs), we analyzed thyroid samples and demonstrated an e nhanced 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 -gamma (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-gamma and synergistically incre ased by TNF-alpha addition. Furthermore, high levels of Ip-10 protein were detected in the supernatants of IFN-gamma -stimulated TFCs. Likewise, Mig p rotein 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-alpha. In a ddition, intrathyroidal lymphocytes from AITD patients showed higher expres sion of CXCR3, CCR2, and CCR5 chemokine receptors than autologous periphera l blood lymphocytes. T lymphoblasts expressing CXCR3 showed an increased mi gration to supernatants from stimulated TFCs, which was abolished by specif ic 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, throug h the production of the chemokines Ip-10, Mig and RANTES, in regulating the recruitment of specific subsets of activated lymphocytes in AITD.