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.
Chen
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K
Department of Internal Medicine, University of Missouri, School of Medicine, Columbia 65212, USA.
Wei
Y
Y
Sharp
G C
GC
Braley-Mullen
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H
D000199:Actins / Q000032:analysis; D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology / Q000473:pathology*; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured / Q000637:transplantation; D003094:Collagen / Q000032:analysis; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis; D006099:Granuloma / Q000473:pathology*; D007114:Immunization; D018664:Interleukin-12 / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D023421:Models, Animal; D012333:RNA, Messenger / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000637:transplantation; D013954:Thyroglobulin / Q000276:immunology; D013961:Thyroid Gland / Q000473:pathology*; D013967:Thyroiditis, Autoimmune / Q000097:blood / Q000276:immunology / Q000473:pathology*; D013974:Thyroxine / Q000097:blood / Q000172:deficiency; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D053773:Transforming Growth Factor beta1
D000199:Actins; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D018664:Interleukin-12; D003094:Collagen; D013954:Thyroglobulin; D013974:Thyroxine