2006 Fiscal Year Final Research Report Summary
Studies on the pathogenesis of Graves' disease and new treatment using our recently established mouse model.
| Project/Area Number |
17590965
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Nagasaki University |
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Principal Investigator |
NAGAYAMA Yuji Nagasaki University, Graduate School of Biomedical Sciences, Department of Medical Gene Technology, Atomic Bomb Disease Institute, professor, 大学院医歯薬学総合研究科, 教授 (30274632)
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| Co-Investigator(Kenkyū-buntansha) |
SAITOH Ohki Nagasaki University, Graduate School of Biomedical Sciences, Department of Medical Gene Technology, Atomic Bomb Disease Institute, research fellow, 大学院医歯薬学総合研究科, 助手 (60380961)
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| Project Period (FY) |
2005 – 2006
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| Keywords | thyroid autoimmunity / thyrotropin receptor / regulatory T cells / autoantibody / Graves' disease / adenovirus |
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| Research Abstract |
1. Suppression of disease development by CD4^+CD25^+ regulatory T cells (Treg) : Depletion of Treg by anti-CD25 antibody induced Graves' hyperthyroidism in 30 % of resistant C57BL/6 mice, and increased serum T_4 levels by 200 % in susceptible BALB/c mice. This effect was attributed to decreased stimulatory antibody titers and increased blocking antibody titers. Furthermore, in transfer experiments to naive wt mice, splenocytes from Graves' mice induced little anti-TSHR antibody, but CD25-depleted splenocytes did low but significant levels of antibody.
2. Suppression of disease development by regulatory cytokines : adenovirus expressing IL-10 or TGF-beta (both are regulatory cytokines) were constructed, and administered to mice together with adenovirus coding the TSHR (Ad-TSHR). Only Ad-IL-10 significantly inhibited hyperthyroidism.
3. Suppression of disease development by apoptosis-inducing Fas ligand (FasL) : Adenovirus expressing FasL was constructed, and infected into dendritic cells (DCs) derived from bone-marrow cells by using GMCSF and IL-4 together with Ad-TSHR. These DCs inhibited anti-TSHR immune response and development of Graves' disease induced by intramuscular injection of Ad-TSHR.
4. TSHR-specific T cell lines are now being established by the TSHR protein and three : peptides which induced IFNgamma release in recall assay. Abilities of individual clones to produce cytokine(s) and to induce hyperthyroidism as well as amino acid sequences of T cell receptors will be studied.
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[Journal Article] BrafV600E promotes invasiveness of thyroid cancer cells through NF-kB activation.2006
Author(s)
Palona I, Namba H, Mitsutake N, Starenki D, Podtchenko A, Sediarou I, Ohtsuru A, Saenko V, Nagayama Y, Umezawa K, Yamashita S.
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Journal Title
Endocrinology. 147(12)
Pages: 5699-5707
Description
「研究成果報告書概要(欧文)」より
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