title: Role of TGFbeta in development of spontaneous autoimmune thyroiditis in NOD.H-2h4 mice.
abstract: Nearly 100% of NOD.H-2h4 mice develop spontaneous autoimmune thyroiditis (SAT) and produce anti-mouse thyroglobulin autoantibodies when they receive 0.05% NaI in their drinking water beginning at 8 wk of age. Our previous studies showed that TGFbeta1 mRNA was constitutively expressed in thyroids and spleens of normal NOD.H-2h4 mice but not other strains of mice. To determine whether TGFbeta might have a role in SAT, mice were given anti-TGFbeta mAb at various times during development of SAT. Anti-TGFbeta markedly inhibited development of SAT and production of anti-mouse thyroglobulin IgG1 autoantibodies. Anti-TGFbeta was most effective in inhibiting SAT when given during the time thyroid lesions were developing, i.e., starting 4 wk after administration of NaI water. The active form of the TGFbeta1 protein was present in thyroids of mice with SAT but not in normal NOD.H-2h4 thyroids. However, thyrocytes of normal NOD.H-2h4 thyroids did express latent TGFbeta1. TGFbeta1 protein expression in the thyroid correlated with SAT severity scores, and administration of anti-TGFbeta inhibited TGFbeta1 protein expression in both the thyroid and spleen. TGFbeta1 was produced primarily by inflammatory cells and was primarily localized in areas of the thyroid containing clusters of CD4(+) T and B cells. Depletion of CD8(+) T cells had no effect on TGFbeta1 protein expression. Activation of splenic T cells was apparently not inhibited by anti-TGFbeta, because up-regulation of mRNA for cytokines and other T cell activation markers was similar for control and anti-TGFbeta-treated mice. TGFbeta1 may function by promoting migration to, or retention of, inflammatory cells in the thyroid.
authors.affiliation: Department of Internal Medicine and Medical Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65212, USA. mullenh@health.missouri.edu
authors.forename: H
authors.initials: H
authors.lastname: Braley-Mullen
authors.forename: K
authors.initials: K
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Wei
authors.forename: S
authors.initials: S
authors.lastname: Yu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D001323:Autoantibodies / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry; D051379:Mice; D016688:Mice, Inbred NOD; D012333:RNA, Messenger / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013954:Thyroglobulin / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D053773:Transforming Growth Factor beta1
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D016207:Cytokines; D012333:RNA, Messenger; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D013954:Thyroglobulin