自己免疫性甲状腺疾患の病態解析研究:遺伝子改変マウスを中心に

• 研究課題/領域番号: 20591099
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 内分泌学
• 研究機関: 長崎大学
• 研究代表者: 永山 雄二 長崎大学, 大学院・医歯薬学総合研究科, 教授 (30274632)
• 研究分担者: 阿比留 教生 長崎大学, 大学院・医歯薬学総合研究科, 助教 (00380981)
• 研究期間 (年度): 2008 – 2010
• 研究課題ステータス: 完了 (2010年度)
• 配分額: 4,680千円 (直接経費: 3,600千円、間接経費: 1,080千円); 2010年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円); 2009年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円); 2008年度: 1,690千円 (直接経費: 1,300千円、間接経費: 390千円)
• キーワード: 甲状腺自己免疫 / TSH受容体 / 橋本病 / バセドウ病

研究概要

遺伝子改変マウス(TSH受容体トランスジェニックマウス、TSH受容体KOマウス、IL-17 KOマウス、AIRE KOマウス)を用いて、自己免疫性甲状腺疾患(バセドウ病、橋本病)の病態解析を行う。

研究成果

• [雑誌論文] Current concentration of artificial radionuclides and estimated radiation doses around the Chernobyl Nuclear Power Plant, the Semipalatinsk Nuclear Testing Site, and in Nagasaki. (2011)
  • 著者名/発表者名: Taira Y, Hayashida N, Brahmanandhan GM, Nagayama Y, Yamashita S, Takahashi J, Gutevitc A, Kozlovsky A, Urazalin M, Takamura N.
  • 雑誌名: J Radiat Res. 52(1) ページ: 88-95
• [雑誌論文] B Cell-Targeted Therapy with anti-CD20 monoclonal antibody in a mouse model of Graves' Hyperthyroidism. (2011)
  • 著者名/発表者名: Ueki I, Abiru N, Kobayashi M, Saitoh O, Ichikawa T, Kerley, Eguchi K, Nagayama Y.
  • 雑誌名: Clin Exp Immunol. 163(3) ページ: 309-317
  • NAID: 120006984774
• [雑誌論文] Differential role of T helper type 17 immune response for Graves' hyperthyroidism in mice with distinct genetic backgrounds. (2011)
  • 著者名/発表者名: Horie I, Abiru N, Saitoh O, Ichikawa T, Iwakura Y, Eguchi K, Nagayama Y.
  • 雑誌名: Autoimmunity. 44(2) ページ: 159-165
• [雑誌論文] Current concentration of artificial radionuclides and estimated radiation doses around the Chernobyl Nuclear Power Plant, the Semipalatinsk Nuclear Testing Site, and in Nagasaki. (2011)
  • 著者名/発表者名: Taira Y, Hayashida N, Brahmanandhan GM, Nagayama Y, Yamashita S, Takahashi J, Gutevitc A, Kozlovsky A, Urazalin M, Takamura N.
  • 雑誌名: Journal of Radiation Research 巻: 52 ページ: 88-95
  • 査読あり
• [雑誌論文] B Cell-Targeted Therapy with anti-CD20 monoclonal antibody in a mouse model of Graves' Hyperthy roidism. (2011)
  • 著者名/発表者名: Ueki I, Abiru N, Kobayashi M, Saitoh O, Ichikawa T, Kerley, Eguchi K, Nagayama Y.
  • 雑誌名: Clinical and Experimental Immunology 巻: 163 ページ: 309-317
  • 査読あり
• [雑誌論文] Differential role of T helper type 17 immune response for Graves' hyperthyroidism in mice with distinct genetic backgrounds. (2011)
  • 著者名/発表者名: Horie I, Abiru N, Saitoh O, Ichikawa T, Iwakura Y, Hguchi K, Nagayama Y.
  • 雑誌名: Autoimmunity 巻: 44 ページ: 159-165
  • 査読あり
• [雑誌論文] The effect of Regulatory T cell depletion on the spectrum of organ-specific autoimmune diseases in non-obese diabetic mice at different ages. (2011)
  • 著者名/発表者名: Nakahara M, Nagayama Y, Ichikawa T, Liping Yu, George S.Eisenbarth, Abiru N.
  • 雑誌名: Autoimmunity 巻: (in press)
  • NAID: 120006985001
  • 査読あり
• [雑誌論文] CHOP deletion does not impact the development of diabetes but suppresses the early production of insulin autoantibody in the NOD mouse (2011)
  • 著者名/発表者名: Satoh T, Abiru N, Kobayashi M, Zhou H, Nakamura K, Kuriya G, Nagayama Y, Kawasaki E, Yamasaki H, Yu L, Eisenbarth GS, Araki E, Mori M, Oyadomari S, Eguchi K.
  • 雑誌名: Apoptosis 巻: (in press)
  • NAID: 120006984789
  • 査読あり
• [雑誌論文] Observations on the proposed "nonclassical" model of autoimmune hypothyroidism. (2010)
  • 著者名/発表者名: Nagayama Y.
  • 雑誌名: Thyroid. 20(6) ページ: 665-666
• [雑誌論文] Enhanced response to mouse thyrotropin (TSH) receptor immunization in TSH knockout mice. (2010)
  • 著者名/発表者名: Nakahara M, Mitsutake N, Sakamoto H, Ichiakwa T, Abiru N, Chen C-R, Rapoport B, McLachlan SM, Nagayama Y.
  • 雑誌名: Endocrinology. 151(8) ページ: 4047-4054
• [雑誌論文] Antibodies to thyroid peroxidase arise spontaneously with age in NOD.H-2^<h4> mice but are not associated with experimentally induced thyroiditis. (2010)
  • 著者名/発表者名: Chen C-R, Hamidi S, Braley-Mullen H, Nagayama Y, Bresee CMS, Rapoport B, McLachlan SM.
  • 雑誌名: Endocrinology. 151(9) ページ: 4583-4593
• [雑誌論文] Observations on the proposed "nonclassical" model of autoimmune hypothyroidism. (2010)
  • 著者名/発表者名: Nagayama Y
  • 雑誌名: Thyroid 巻: 20 ページ: 665-666
  • 査読あり
• [雑誌論文] Enhanced response to mouse thyrotropin (TSH) receptor immunization in TSH knockout mice. (2010)
  • 著者名/発表者名: Nakahara M, Mitsutake N, Sakamoto H, Ichiakwa T, Abiru N, Chen C-R, Rapoport B, McLachlan SM, Nagayama Y.
  • 雑誌名: Endocrinology 巻: 151 ページ: 4047-4054
  • 査読あり
• [雑誌論文] Antibodies to thyroid peroxidase arise spontaneously with age in NOD.H-2h4 mice but are not associated with experimentally induced thyroiditis. (2010)
  • 著者名/発表者名: Chen C-R, Hamidi S, Braley-Mullen H, Nagayama Y, Bresee CMS, Rapoport B, McLachlan SM.
  • 雑誌名: Endocrinology 巻: 151 ページ: 4583-4593
  • 査読あり
• [雑誌論文] Expression of immuno-regulatory molecules on the thyrocytes protects NOD-H2^<h4> mice from developing autoimmune thyroiditis. (2009)
  • 著者名/発表者名: Nakahara M, Nagayama Y, Sogawa R, Saitoh O, Tone S, Abiru N.
  • 雑誌名: Endocrinology. 150(3) ページ: 1545-1551
• [雑誌論文] Studies in mice deficient for the Autoimmune Regulator (Aire) and transgenic for the thyrotropin receptor reveal a role for Aire in tolerance for thyroid autoantigens. (2009)
  • 著者名/発表者名: Misharin A, Aliesky H, Nagayama Y, Rapoport B, McLachlan SM.
  • 雑誌名: Endocrinology. 150(6) ページ: 2948-2956
• [雑誌論文] Attenuation of induced hyperthyroidism in mice by pre-treatment with thyrotropin receptor protein : diversion of thyroid stimulating antibody to non-functional antibody induction. (2009)
  • 著者名/発表者名: Misharin AV, Nagayama Y, Holly A. Aliesky AH, Mizutori Y, Rapoport B, McLachlan SM.
  • 雑誌名: Endocrinology. 150(8) ページ: 3944-3952
• [雑誌論文] Fibroblast- mediated in vivo and in vitro growth promotion of thyroid carcinoma FTRL-Tc, not normal thyroid FRTL5, cells. (2009)
  • 著者名/発表者名: Saitoh O, Mitsutake N, Nakayama T, Nagayama Y.
  • 雑誌名: Thyroid. 19(7) ページ: 735-742
• [雑誌論文] T helper type 17 immune response plays an indispensable role for development of experimental autoimmune thyroiditis in NOD-H2^<h4> mice. (2009)
  • 著者名/発表者名: Horie I, Abiru N, Nagayama Y, Saitoh O, Ichikawa T, Iwakura Y, Eguchi K.
  • 雑誌名: Endocrinology. 150(11) ページ: 5135-5142
• [雑誌論文] Induction of late-onset, spontaneous autoimmune thyroiditis by a single low-dose irradiation in non-obese diabetic-H2^<h4> mice. (2009)
  • 著者名/発表者名: Nagayama Y, Ichikawa T, Saitoh O, Abiru N.
  • 雑誌名: J Radiat Res. 50(6) ページ: 573-577
• [雑誌論文] Expression of immuno-regulatory molecules on the thyrocytes protects NOD-H2^<h4> mice from developing autoimmune thyroiditis (2009)
  • 著者名/発表者名: Nakahara M, Nagayama Y, Sogawa R, Saitoh O, Tone S, Abiru N.
  • 雑誌名: Endocrinology 150 ページ: 1545-1551
  • 査読あり
• [雑誌論文] Studies in mice deficient for the Autoimmune Regulator(Aire)and transgenic for the thyrotropin receptor reveal a role for Aire in tolerance for thyroid autoantigens (2009)
  • 著者名/発表者名: Misharin A, Aliesky H, Nagayama Y, Rapoport B, McLachlan SM.
  • 雑誌名: Endocrinology 150 ページ: 2948-2956
  • 査読あり
• [雑誌論文] Attenuation of induced hyperthyroidism in mice by pre-treatment with thyrotropin receptor protein : diversion of thyroid stimulating antibody to non-functional antibody induction. (2009)
  • 著者名/発表者名: Misharin AV, Nagayama Y, Holly A.Aliesky AH, Mizutori Y, Rapoport B, McLachlan SM.
  • 雑誌名: Endocrinology 150 ページ: 3944-3952
  • 査読あり
• [雑誌論文] Fibroblast-mediated in vivo and in vitro growth promotion of thyroid carcinoma FTRL-Tc, not normal thyroid FRTL5, cells. (2009)
  • 著者名/発表者名: Saitoh O, Mitsutake N, Nakayama T, Nagayama Y.
  • 雑誌名: Thyroid 19 ページ: 735-742
  • 査読あり
• [雑誌論文] T helper type 17 immune response plays an indispensable role for development of experimental autoimmune thyroiditis in NOD-H2^<h4> mice. (2009)
  • 著者名/発表者名: Horie I, Abiru N, Nagayama Y, Saitoh O, Ichikawa T, Iwakura Y, Eguchi K.
  • 雑誌名: Endocrinology 150 ページ: 5135-5142
  • 査読あり
• [雑誌論文] Induction of late-onset, spontaneous autoimmune thyroiditis by a single low-dose irradiation in non-obese diabetic-H2^<h4> mice. (2009)
  • 著者名/発表者名: Nagayama Y, Ichikawa T, Saitoh O, Abiru N.
  • 雑誌名: Journal of Radiation Research 50 ページ: 573-577
  • 査読あり
• [雑誌論文] Combined activation of innate and adaptive immunity with polyinosinic- polycytidylic acid and insulin B:9-23 self-peptide in the genetically susceptible NOD mouse : differential effects on insulitis and diabetes progression. (2008)
  • 著者名/発表者名: Fukushima K, Kobayashi M, Nagayama Y, Satoh T, Nakahara M, Kawasaki E, Yamasaki H, Ueha S, Matsushima K, Liu E, Eisenbarth GS, Eguchi K, Abiru N.
  • 雑誌名: Biochem Biophys Res Commun. 367(4) ページ: 719-724
• [雑誌論文] Exacerbation of autoimmune thyroiditis by a single dose of whole body irradiation in NOD-H2h4 mice. (2008)
  • 著者名/発表者名: Nagayama Y, Kaminoda K, Mizutori Y, Saitoh O, Abiru N.
  • 雑誌名: Int J Radiat Biol. 84(9) ページ: 761-769
• [雑誌論文] Role of the human A-subunit in transgenic mice that develop thyroid lymphocytic infiltration after immunization and regulatory T cell depletion. (2008)
  • 著者名/発表者名: Mizutori Y, Nagayama Y, Flower D, Misharin A, Aliesky HA, Rapoport B, McLachlan SM.
  • 雑誌名: Clin Exp Immunol. 154(3) ページ: 305-315
• [雑誌論文] Combined activation of innate and adaptive immunity with polyinosinic-polycytidylic acid and insulin B : 9-23 self-peptide in the genetically susceptible NOD mouse : differential effects on insulitis and diabetes progression. (2008)
  • 著者名/発表者名: Fukushima K, Kobayashi M, Nagayama Y, et al.
  • 雑誌名: Biochem Biophys Res Commun. 367 ページ: 719-724
  • 査読あり
• [雑誌論文] Exacerbation of autoimmune thyroiditis by a singledose of whole body irradiation in NOD-H2^<h4> mice. (2008)
  • 著者名/発表者名: Nagayama Y, et al.
  • 雑誌名: Int J Radiat Biol. 84 ページ: 761-769
  • 査読あり
• [雑誌論文] Role of the human A-subunit in transgenic mice that develop thyroid lymphocytic infiltration after immunization and regulatory T cell depletion. (2008)
  • 著者名/発表者名: Mizutori Y, Nagayama Y, et al.
  • 雑誌名: Clin Exp Immunol. 154 ページ: 305-315
  • 査読あり
• [雑誌論文] The effect of Regulatory T cell depletion on the spectrum of organ-specific autoimmune diseases in non-obese diabetic mice at different ages.
  • 著者名/発表者名: Nakahara M, Nagayama Y, Ichikawa T, Liping Yu, George S. Eisenbarth, Abiru N.
  • 雑誌名: Autoimmunity. in press.
  • NAID: 120006985001
• [雑誌論文] CHOP deletion does not impact the development of diabetes but suppresses the early production of insulin autoantibody in the NOD mouse.
  • 著者名/発表者名: Satoh T, Abiru N, Kobayashi M, Zhou H, Nakamura K, Kuriya G, Nagayama Y, Kawasaki E, Yamasaki H, Yu L, Eisenbarth GS, Araki E, Mori M, Oyadomari S, Eguchi K.
  • 雑誌名: Apoptosis. in press.
  • NAID: 120006984789
• [学会発表] Animal models of Graves' diseases. (2010)
  • 著者名/発表者名: Nagayama Y
  • 学会等名: International Thyroid Congress
  • 発表場所: Paris
  • 年月日: 2010-09-12
• [学会発表] Enhanced response to mouse thyrotropin (TSH) receptor immunization in TSH receptor knockout mice. (2010)
  • 著者名/発表者名: Nakahara M, Nagayama Y
  • 学会等名: The 14th International Thyroid Congress
  • 発表場所: Paris, France
• [学会発表] Immunization of C57BL/6 and BALB/C with adenoviral TSHR289 casuses significant infiltration of orbital tissues with macrophages and T-lymphocytes. (2010)
  • 著者名/発表者名: Johnson KT, Ziler B, Thanos M, Carpinteiro A, Schmid KW, Minich W, Gulbins E, Nagayama Y, Eckstein AK
  • 学会等名: International Thyroid Congress
  • 発表場所: Paris, France
• [学会発表] Human versus Mouse Thyrotropin Receptor as an Autoantigen in a Mouse Model of Graves' Hyperthyroidism. (2010)
  • 著者名/発表者名: 永山雄二
  • 学会等名: International Society of Endocrinology
  • 発表場所: Kyoto, Japan
• [学会発表] Animal models of Graves' diseases. (2010)
  • 著者名/発表者名: 永山雄二
  • 学会等名: (symposium) International Thyroid Congress
  • 発表場所: Paris, France
• [学会発表] マウスバセドウ病モデルにおける免疫反応とトレランス (2010)
  • 著者名/発表者名: 永山雄二
  • 学会等名: 第32回京都甲状腺研究会
  • 発表場所: 京都
• [学会発表] マウス甲状腺自己免疫疾患の病態解析-免疫反応とトレランス- (2010)
  • 著者名/発表者名: 永山雄二
  • 学会等名: 第8回1型糖尿病研究会
  • 発表場所: 長崎
• [学会発表] 理想的な甲状腺癌マウスモデルの作製 (2010)
  • 著者名/発表者名: 永山雄二
  • 学会等名: 第53回日本甲状腺学会
  • 発表場所: 長崎
• [学会発表] バセドウ病マウスモデルにおけるT helper 17(Th17)の病態形成への関与の検討 (2009)
  • 著者名/発表者名: 植木郁子、阿比留教生、江口勝美、永山雄二
  • 学会等名: 日本免疫学会
  • 発表場所: 名古屋
  • 年月日: 2009-12-03
• [学会発表] NODマウスにおけるエフェクターT細胞の標的臓器及び制御性T細胞への感受性の加齢に伴う変化 (2009)
  • 著者名/発表者名: 中原麻美、永山雄二、阿比留教生
  • 学会等名: 日本免疫学会
  • 発表場所: 名古屋
  • 年月日: 2009-12-02
• [学会発表] バセドウ病マウスモデルにおけるT helper 17(Th17)の病態形成への関与の検討 (2009)
  • 著者名/発表者名: 堀江一郎、斉藤巨樹、阿比留教生、厨源平、江口勝美、永山雄二
  • 学会等名: 日本甲状腺学会
  • 発表場所: 名古屋
  • 年月日: 2009-11-05
• [学会発表] Recent advances of mouse models of autoimmune disease (2009)
  • 著者名/発表者名: 永山雄二
  • 学会等名: 日本甲状腺学会
  • 発表場所: 名古屋
  • 年月日: 2009-11-04
• [学会発表] バセドウ病マウスモデルにおけるB細胞/形質細胞標的治療の基礎研究 (2009)
  • 著者名/発表者名: 植木郁子、阿比留教生、古林正和、斉藤巨樹、江口勝美、永山雄二
  • 学会等名: 日本甲状腺学会
  • 発表場所: 名古屋
  • 年月日: 2009-11-04
• [学会発表] Introduction of our global COE program titled "Global Strategic Center for Radiation Health Risk Control". (2009)
  • 著者名/発表者名: 永山雄二
  • 学会等名: 5^<th> International scientific- practical conference <<ECOLOGY, RADIATION AND HEALTH>>
  • 発表場所: Semipalatinsk, Kazakhstan
• [学会発表] Recent Advances in Studies on Mouse Models of Autoimmune Thyroid Disease. (2009)
  • 著者名/発表者名: 永山雄二
  • 学会等名: International Symposium on Molecular Thyroidology
  • 発表場所: Nagoya
• [学会発表] Fibroblast-Mediated Growth Promotion of Thyroid Carcinoma FRTL-Tc Cells. (2009)
  • 著者名/発表者名: Saitoh O, Mitsutake N, Nagayama Y
  • 学会等名: The 91th Meeting of Endocrine Society
  • 発表場所: Washington DC, USA
• [学会発表] Different Roles of T Helper Type 17 Immune Response in Experimental Graves' Hyperthyroidism Induced in BALB/c and NOD-H2h4 Mice. (2009)
  • 著者名/発表者名: Horie I, Saitoh O, Abiru N, Nagayama Y
  • 学会等名: The 91th Meeting of Endocrine Society
  • 発表場所: Washington DC, USA
• [学会発表] Age-dependent Alteration in a Spectrum of Organ-Specific Autoimmune Diseases in Nonobese Diabetic Mice. (2009)
  • 著者名/発表者名: Nakahara M, Abiru N, Nagayama Y
  • 学会等名: The 91th Meeting of Endocrine Society
  • 発表場所: Washington DC, USA
• [学会発表] Granzyme B Deficiency Reduces Cyclophosphamide Induced Diabetes, But Not Spontaneous Diabetes in nonobese diabetic (NOD) mice. (2009)
  • 著者名/発表者名: Kobayashi M, Kaneko C, Abiru N, Kan Nakamura, Kuriya G, Satoh T, Kawasaki E, Yamasaki H, Nagayama Y, Eguchi K
  • 学会等名: IDS 10
  • 発表場所: Sweden
• [学会発表] Loss of IL-17 does not impact on the development of diabetes, but reduces the expression of insulin autoantibodies in NOD mice. (2009)
  • 著者名/発表者名: Kuriya G, Abiru N, Nagayama Y, Nakamura K, Sato T, Kobayashi M, Kawasaki E, Yamasaki H, Iwakura Y, Eguchi K
  • 学会等名: IDS 10
  • 発表場所: Sweden
• [学会発表] Recent advances of mouse models of autoimmune disease. (2009)
  • 著者名/発表者名: 永山雄二
  • 学会等名: 第52回日本甲状腺学会
  • 発表場所: 名古屋
• [学会発表] Mouse models of Graves' disease (2008)
  • 著者名/発表者名: Nagayama Y.
  • 学会等名: 13^<th> International Congress of Endocrinology
  • 発表場所: Rio de Janeiro, Bz
  • 年月日: 2008-11-11
• [学会発表] Recent advances in mouse models of Graves' hyperthyroidism (symposium). (2008)
  • 著者名/発表者名: 永山雄二
  • 学会等名: Korean Thyroid Meeting
  • 発表場所: Gwangju, South Korea
• [学会発表] Mouse models of Graves' disease. (2008)
  • 著者名/発表者名: 永山雄二
  • 学会等名: International Society of Endocrinology
  • 発表場所: Rio de Janeiro, Brazil
• [学会発表] Aire-deficiency modulates induction of TSHR antibodies and hyperthyroidism in a mouse model of Graves' disease. (2008)
  • 著者名/発表者名: Misharin A, Aliesky H, Nagayama Y, Rapoport B, McLachlan SM
  • 学会等名: The 90th Meeting of Endocrine Society
  • 発表場所: San Francisco, USA
• [学会発表] 自己免疫性甲状腺疾患マウスモデルの開発と最近の新知見 (2008)
  • 著者名/発表者名: 永山雄二
  • 学会等名: 第24回甲状腺病態生理研究会
  • 発表場所: 東京
• [図書] Immunoendocrinology : Scientific and Clinical Aspects.(Animal models of autoimmune thyroid disease.(In))(Eisenbarth G (ed)) (2011)
  • 著者名/発表者名: Nagayama Y.
  • 出版者: Humana Press
• [図書] Animal models of autoimmune thyroid disease. (In) Immunoendocrinology : Scientific and Clinical Aspects. (2011)
  • 著者名/発表者名: Nagayama Y
  • 総ページ数: 12
  • 出版者: Humana Press
• [図書] The Proceeding for 13th International Congress of Endocrinology.(Mouse models of Graves' disease) (2008)
  • 著者名/発表者名: Nagayama Y.
• [図書] The Proceeding for 13th International Congress of Endocrinology. (2008)
  • 著者名/発表者名: Nagayama Y.
  • 出版者: MEDIMOND INTERNATIONAL PROCEEDING
• [備考] ホームページ等
  • URL: http://www-sdc.med.nagasaki-u.ac.jp/genetech/genkenbunshi/index.htm