title: Interleukin 10 deficiency attenuates induction of anti-TSH receptor antibodies and hyperthyroidism in a mouse Graves' model.
abstract: Experimental Graves'-like hyperthyroidism can be induced in susceptible mouse strains by repetitive immunizations with recombinant adenovirus expressing the human full-length TSH receptor (TSHR) or its A-subunit. Previous studies have shown that splenocytes from immunized mice produce interferon (IFN)-γ and interleukin (IL) 10 in response to antigen stimulation in an in vitro T cell recall assay. Although IFN-γ is now well known to be essential for disease induction, the role(s) played by IL10 are unknown. Therefore, this study was conducted to clarify the significance of endogenous IL10 in the pathogenesis of experimental Graves' disease using IL10 deficient (IL10(-/-)) mice. Our results show that T cell response was augmented when estimated by their antigen-specific secretion of the key cytokine IFN-γ, but B cell function was dampened, that is, anti-TSHR antibody titers were decreased in IL10(-/-) mice, resulting in a lower incidence of Graves' hyperthyroidism (54% in IL10(+/+) vs 25% in IL10(-/-)). Thus, in addition to IFN-γ, these data clarified the role of IL10 for optimizing anti-TSHR antibody induction and eliciting Graves' hyperthyroidism in our Graves' mouse model.
authors.affiliation: Department of Molecular Medicine, Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ueki
authors.forename: Norio
authors.initials: N
authors.lastname: Abiru
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kawagoe
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nagayama
mesh_terms: D000818:Animals; D000906:Antibodies; D001402:B-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D006111:Graves Disease / Q000209:etiology* / Q000276:immunology; D006801:Humans; D006980:Hyperthyroidism / Q000209:etiology* / Q000276:immunology; D007371:Interferon-gamma; D016753:Interleukin-10 / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D011989:Receptors, Thyrotropin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000906:Antibodies; D011989:Receptors, Thyrotropin; D016753:Interleukin-10; D007371:Interferon-gamma