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2010 Fiscal Year Annual Research Report

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

Research Project

Project/Area Number 20591099
Research InstitutionNagasaki University

Principal Investigator

永山 雄二  長崎大学, 医歯(薬)学総合研究科, 教授 (30274632)

Co-Investigator(Kenkyū-buntansha) 阿比留 教生  長崎大学, 医歯(薬)学総合研究科, 講師 (00380981)
Keywords甲状腺自己免疫 / TSH受容体 / 橋本病 / バセドウ病
Research Abstract

1.自己免疫性甲状腺疾患におけるTh17の重要性検討の中で、BALB/cマウスでのバセドウ病発症はTh17非依存性である事を以前見出したが、今回NOD-H2^<h4>マウスではTh17依存性である事、即ちエフェクターT細胞の重要性はマウス系で異なる事を見出した。これはヒトでの病態のheterogeneityを反映していると考えられる。
2.マウスにおいてはマウスTSH受容体への寛容が非常に強力であるが、TSH受容体KOマウスでは明らかな免疫反応が見られる事を以前見出したが、これをバセドウ病モデル作製へ結び付けるために、TSH受容体KOマウスの脾細胞のヌードマウスへのトランスファー実験を行った。免疫したTSH受容体KOマウスからの脾細胞はヌードマウスにおいて、6カ月にわたり抗TSH受容体抗体を産生し、非免疫TSH受容体KOマウスからの脾細胞はトランスファーのみでは抗体産生しなかったが、co-inhibitory moleculeであるCTLA4に対する抗体投与によって自然に抗体を産生することを見出した。これはある意味TSH受容体自己免疫の自然発症モデルと言え、今後の関東破綻機序解明に非常に有用なモデルができたと考えられる。

  • Research Products

    (11 results)

All 2011 2010

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (2 results) Book (1 results)

  • [Journal Article] Current concentration of artificial radionuclides and estimated radiation doses around the Chernobyl Nuclear Power Plant, the Semipalatinsk Nuclear Testing Site, and in Nagasaki.2011

    • Author(s)
      Taira Y, Hayashida N, Brahmanandhan GM, Nagayama Y, Yamashita S, Takahashi J, Gutevitc A, Kozlovsky A, Urazalin M, Takamura N.
    • Journal Title

      Journal of Radiation Research

      Volume: 52 Pages: 88-95

    • Peer Reviewed
  • [Journal Article] B Cell-Targeted Therapy with anti-CD20 monoclonal antibody in a mouse model of Graves' Hyperthy roidism.2011

    • Author(s)
      Ueki I, Abiru N, Kobayashi M, Saitoh O, Ichikawa T, Kerley, Eguchi K, Nagayama Y.
    • Journal Title

      Clinical and Experimental Immunology

      Volume: 163 Pages: 309-317

    • Peer Reviewed
  • [Journal Article] Differential role of T helper type 17 immune response for Graves' hyperthyroidism in mice with distinct genetic backgrounds.2011

    • Author(s)
      Horie I, Abiru N, Saitoh O, Ichikawa T, Iwakura Y, Hguchi K, Nagayama Y.
    • Journal Title

      Autoimmunity

      Volume: 44 Pages: 159-165

    • Peer Reviewed
  • [Journal Article] The effect of Regulatory T cell depletion on the spectrum of organ-specific autoimmune diseases in non-obese diabetic mice at different ages.2011

    • Author(s)
      Nakahara M, Nagayama Y, Ichikawa T, Liping Yu, George S.Eisenbarth, Abiru N.
    • Journal Title

      Autoimmunity

      Volume: (in press)

    • Peer Reviewed
  • [Journal Article] CHOP deletion does not impact the development of diabetes but suppresses the early production of insulin autoantibody in the NOD mouse2011

    • Author(s)
      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.
    • Journal Title

      Apoptosis

      Volume: (in press)

    • Peer Reviewed
  • [Journal Article] Observations on the proposed "nonclassical" model of autoimmune hypothyroidism.2010

    • Author(s)
      Nagayama Y
    • Journal Title

      Thyroid

      Volume: 20 Pages: 665-666

    • Peer Reviewed
  • [Journal Article] Enhanced response to mouse thyrotropin (TSH) receptor immunization in TSH knockout mice.2010

    • Author(s)
      Nakahara M, Mitsutake N, Sakamoto H, Ichiakwa T, Abiru N, Chen C-R, Rapoport B, McLachlan SM, Nagayama Y.
    • Journal Title

      Endocrinology

      Volume: 151 Pages: 4047-4054

    • Peer Reviewed
  • [Journal Article] Antibodies to thyroid peroxidase arise spontaneously with age in NOD.H-2h4 mice but are not associated with experimentally induced thyroiditis.2010

    • Author(s)
      Chen C-R, Hamidi S, Braley-Mullen H, Nagayama Y, Bresee CMS, Rapoport B, McLachlan SM.
    • Journal Title

      Endocrinology

      Volume: 151 Pages: 4583-4593

    • Peer Reviewed
  • [Presentation] 理想的な甲状腺癌マウスモデルの作製2010

    • Author(s)
      永山雄二
    • Organizer
      第53回日本甲状腺学会
    • Place of Presentation
      長崎
    • Year and Date
      20100000
  • [Presentation] Animal models of Graves' diseases.2010

    • Author(s)
      Nagayama Y
    • Organizer
      International Thyroid Congress
    • Place of Presentation
      Paris
    • Year and Date
      2010-09-12
  • [Book] Animal models of autoimmune thyroid disease. (In) Immunoendocrinology : Scientific and Clinical Aspects.2011

    • Author(s)
      Nagayama Y
    • Total Pages
      12
    • Publisher
      Humana Press

URL: 

Published: 2012-07-19  

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