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

J Clin Endocrinol Metab. 2001 Oct;86(10):5008-16. doi: 10.1210/jcem.86.10.7953.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement
  • Chemokine CCL2 / biosynthesis
  • Chemokine CCL5 / biosynthesis
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines, CXC / biosynthesis*
  • Chemokines, CXC / genetics
  • Graves Disease / immunology*
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Lymphocytes / physiology*
  • Receptors, CXCR3
  • Receptors, Chemokine / analysis*
  • Thyroid Gland / cytology
  • Thyroid Gland / metabolism*
  • Thyroiditis, Autoimmune / immunology*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • CXCL9 protein, human
  • CXCR3 protein, human
  • Chemokine CCL2
  • Chemokine CCL5
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines, CXC
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-1
  • Receptors, CXCR3
  • Receptors, Chemokine
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma