Immune mechanisms in thyroid eye disease

Thyroid. 2008 Sep;18(9):959-65. doi: 10.1089/thy.2007.0407.

Abstract

Thyroid eye disease (TED) is an inflammatory condition of the orbit closely associated with Graves' disease. During the course of TED, fibrosis can develop around the extraocular muscles, and excess extracellular matrix and fat accumulates in the periorbital space. This dramatic remodeling results in protrusion of the eye, also known as exophthalmos. Current treatments are sometimes effective in alleviating the symptoms of the disease, but there remains a demand for treatments that prevent or reverse the pathological alterations of orbital tissues. Such treatments may become available as a result of research aimed at understanding the mechanism by which Graves' disease leads to specific remodeling of orbital tissues. Recent findings have uncovered the importance of intercellular communication between autoreactive T cells and orbital fibroblasts. When orbital fibroblasts are activated, possibly by Graves' disease-related autoantibodies, they release T cell chemoattractants, initiating an interaction in which these cells activate each other. These interactions ultimately result in fibroblasts expressing extracellular matrix molecules, proliferating and differentiating into myofibroblasts or lipofibroblasts. Although the mechanisms underlying these processes are not completely understood, several currently available therapeutic strategies might interrupt the signaling between B and T cells and fibroblasts, thereby treating the clinical manifestations of TED.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adipocytes / metabolism
  • Autoantibodies / immunology
  • Autoantigens / immunology
  • Autoimmunity / immunology
  • Cell Differentiation
  • Cell Proliferation
  • Disease Progression
  • Extracellular Matrix / metabolism
  • Eye Diseases / immunology
  • Eye Diseases / physiopathology
  • Fibroblasts / metabolism
  • Graves Ophthalmopathy / immunology*
  • Graves Ophthalmopathy / physiopathology*
  • Humans
  • Models, Biological
  • Orbit / immunology
  • T-Lymphocytes / metabolism

Substances

  • Autoantibodies
  • Autoantigens