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 vi tro with thyroglobulin, anti-IL-2R, and IL-12, There was almost complete de struction of thyroid follicles, leading to fibrosis of the gland and reduce d serum T4 levels. Fibrosis was confirmed by staining for collagen and alph a smooth-muscle actin, a marker of myofibroblasts. Kinetic studies characte rized the onset and development of thyroid fibrosis. TGF-beta1 was increase d at mRNA and protein levels, and expression of TGF-beta1 protein parallele d G-EAT severity. Comparison of staining patterns showed that TGF-beta1 was expressed in areas of myofibroblast and collagen accummulation, implying t hat TGF-beta1 may play a role in fibrosis in G-EAT, Further studies demonst rated that myofibroblasts, macrophages, and thyrocytes contributed to TGF-b eta1 production. This provides an excellent model to study the mechanisms o f fibrosis associated with autoimmune damage.