title: Dual roles for IFN-gamma, but not for IL-4, in spontaneous autoimmune thyroiditis in NOD.H-2h4 mice.
abstract: Spontaneous autoimmune thyroiditis (SAT) is an organ-specific autoimmune disease characterized by chronic inflammation of the thyroid by T and B lymphocytes. To investigate the roles of Th1 and Th2 cytokines in the pathogenesis of SAT, IFN-gamma(-/-) and IL-4(-/-) NOD.H-2h4 mice were generated. IL-4(-/-) mice developed lymphocytic SAT (L-SAT) comparable to that of wild-type (WT) mice. They produced little anti-mouse thyroglobulin (MTg) IgG1, but had levels of anti-MTg IgG2b comparable to WT mice. Compared with WT mice, IFN-gamma(-/-) mice produced significantly less anti-MTg IgG1 and IgG2b. Absence of IFN-gamma resulted in abnormal proliferation of thyroid epithelial cells with minimal lymphocyte infiltration. Thyroids of IFN-gamma(-/-) mice had markedly reduced B lymphocyte chemoattractant expression, B cell and plasma cell infiltration, and decreased MHC class II expression on thyrocytes compared with WT mice. Adoptive transfer of WT splenocytes to IFN-gamma(-/-) mice restored the capacity to develop typical L-SAT, enhanced anti-MTg IgG1 and IgG2b production, up-regulated MHC class II expression on thyrocytes and decreased thyrocyte proliferation. These results suggest that IFN-gamma plays a dual role in the development of SAT. IFN-gamma is required for development of L-SAT, and it also functions to inhibit thyroid epithelial cell proliferation.
authors.affiliation: Department of. Internal Medicine, University of Missouri School of Medicine, Columbia, MO 65212, USA.
authors.forename: Shiguang
authors.initials: S
authors.lastname: Yu
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Sharp
authors.forename: Helen
authors.initials: H
authors.lastname: Braley-Mullen
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D010950:Plasma Cells / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D016176:T-Lymphocyte Subsets / Q000473:pathology; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: D001323:Autoantibodies; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; C006606:anti-thyroglobulin; D015847:Interleukin-4; D007371:Interferon-gamma