Mechanisms and kinetics of proliferation and fibrosis development in a mouse model of thyrocyte hyperplasia

Cell Immunol. 2016 Jun-Jul:304-305:16-26. doi: 10.1016/j.cellimm.2016.04.006. Epub 2016 Apr 22.


IFN-γ(-/-) NOD.H-2h4 mice develop autoimmune disease with extensive hyperplasia and proliferation of thyroid epithelial cells (TEC H/P) and fibrosis. Splenic T cells from donors with severe TEC H/P transfer TEC H/P to SCID recipients. The goal of this study was to determine what factors control TEC H/P development/progression by examining T cells, markers of apoptosis, senescence and proliferation in thyroids of SCID recipients over time. At 28days, T cell infiltration was maximal, thyrocytes were proliferating, and fibrosis was moderate. At days 60 and 90, thyroids were larger with more fibrosis. T cells, cytokines and thyrocyte proliferation decreased, and cell cycle inhibitor proteins, and anti-apoptotic molecules increased. T cells and thyrocytes had foci of phosphorylated histone protein H2A.X, indicative of cellular senescence, when TEC H/P progressed and thyrocyte proliferation declined. Some thyrocytes were regenerating at day 90, with irregularly shaped empty follicles and ciliated epithelium. Proliferating thyrocytes were thyroid transcription factor (TTF1)-positive, suggesting they derived from epithelial cells and not brachial cleft remnants.

Keywords: Autoimmunity; Fibrosis; Senescence; Thyrocyte proliferation; Thyroid epithelial cell (thyrocyte) hyperplasia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Cellular Senescence
  • Cytokines / metabolism
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Fibrosis
  • Histones / metabolism*
  • Humans
  • Hyperplasia
  • Interferon-gamma / genetics
  • Mice
  • Mice, Knockout
  • Mice, SCID
  • T-Lymphocytes / immunology*
  • Thyroid Epithelial Cells / metabolism*
  • Thyroid Epithelial Cells / pathology
  • Thyroid Gland / pathology*
  • Thyroiditis, Autoimmune / metabolism*
  • Thyroiditis, Autoimmune / pathology
  • Transcription Factors


  • Cytokines
  • DNA-Binding Proteins
  • H2AX protein, mouse
  • Histones
  • Transcription Factors
  • Ttf1 protein, mouse
  • Interferon-gamma