Characterization of thyroid fibrosis in a murine model of granulomatous experimental autoimmune thyroiditis.

This study was initiated to identify and characterize thyroid fibrosis in a murine model of granulomatous experimental autoimmune thyroiditis (G-EAT) and determine if TGF-beta1 might be involved in fibrosis. G-EAT was induced by transfer of mouse thyroglobulin-sensitized spleen cells activated in vitro with thyroglobulin, anti-IL-2R, and IL-12. There was almost complete destruction of thyroid follicles, leading to fibrosis of the gland and reduced serum T4 levels. Fibrosis was confirmed by staining for collagen and alpha smooth-muscle actin, a marker of myofibroblasts. Kinetic studies characterized the onset and development of thyroid fibrosis. TGF-1beta was increased at mRNA and protein levels, and expression of TGF-beta1 protein paralleled G-EAT severity. Comparison of staining patterns showed that TGF-beta1 was expressed in areas of myofibroblast and collagen accumulation, implying that TGF-beta1 may play a role in fibrosis in G-EAT. Further studies demonstrated that myofibroblasts, macrophages, and thyrocytes contributed to TGF-beta1 production. This provides an excellent model to study the mechanisms of fibrosis associated with autoimmune damage.