Thyroid epithelial cell hyperplasia in IFN-gamma deficient NOD.H-2h4 mice.
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.
Yu
Shiguang
S
Department of Internal Medicine, Division of Immunology and Rheumatology, University of Missouri-Columbia, NE307 Health Science Center, One Hospital Drive, Columbia, MO 65212, USA.
Sharp
Gordon C
GC
Braley-Mullen
Helen
H
D000818:Animals; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology*; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology*; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D012974:Sodium Iodide / Q000494:pharmacology; D013961:Thyroid Gland / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology
D007371:Interferon-gamma; D012974:Sodium Iodide