title: Thyrocytes from autoimmune thyroid disorders produce the chemokines IP-10 and Mig and attract CXCR3+ lymphocytes.
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-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 increased by TNF-alpha addition. Furthermore, high levels of Ip-10 protein were detected in the supernatants of IFN-gamma-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-alpha. 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.
authors.affiliation: Department of Endocrinology, Hospital de la Princesa, Universidad Autónoma, Madrid 28006, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: García-López
authors.forename: D
authors.initials: D
authors.lastname: Sancho
authors.forename: F
authors.initials: F
authors.lastname: Sánchez-Madrid
authors.forename: M
authors.initials: M
authors.lastname: Marazuela
mesh_terms: D002465:Cell Movement; D018932:Chemokine CCL2 / Q000096:biosynthesis; D018946:Chemokine CCL5 / Q000096:biosynthesis; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008214:Lymphocytes / Q000502:physiology*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis*; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D013967:Thyroiditis, Autoimmune / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma