Thyroid epithelial cell hyperplasia in IFN-gamma deficient NOD.H-2h4 mice

Clin Immunol. 2006 Jan;118(1):92-100. doi: 10.1016/j.clim.2005.07.013. Epub 2005 Sep 16.


The role of inflammatory cells in thyroid epithelial cell (thyrocyte) hyperplasia is unknown. Here, we demonstrate that thyrocyte hyperplasia in IFN-gamma-/- NOD.H-2h4 mice has an autoimmune basis. After chronic exposure to increased dietary iodine, 60% of IFN-gamma-/- mice had severe thyrocyte hyperplasia with minimal or moderate lymphocyte infiltration, and thyroid dysfunction with reduced serum T4. All mice produced anti-thyroglobulin autoantibody. Some wild-type NOD.H-2h4 mice had isolated areas of thyrocyte hyperplasia with predominantly lymphocytic infiltration, whereas IL-4-/- and 50% of wild-type NOD.H-2h4 mice developed lymphocytic thyroiditis but no thyrocyte hyperplasia. Both thyroid infiltrating inflammatory cells and environmental factors (iodine) were required to induce thyrocyte hyperplasia. Splenocytes from IFN-gamma-/- mice with thyrocyte hyperplasia, but not splenocytes from naïve IFN-gamma-/- mice, induced hyperplasia in IFN-gamma-/- NOD.H-2h4.SCID mice. These results may provide clues for understanding the mechanisms underlying development of epithelial cell hyperplasia not only in thyroids but also in other tissues and organs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology*
  • Hyperplasia / genetics
  • Hyperplasia / pathology*
  • Interferon-gamma / deficiency
  • Interferon-gamma / genetics
  • Interferon-gamma / physiology*
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Sodium Iodide / pharmacology
  • Thyroid Gland / immunology*
  • Thyroid Gland / metabolism
  • Thyroid Gland / pathology*
  • Thyroiditis, Autoimmune / immunology


  • Interferon-gamma
  • Sodium Iodide