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Therapy of rheumatoid arthritis by S1P receptor antagonisit and IL-2/IL-2 antibody immune complex

Research Project

Project/Area Number 15K09538
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionHyogo Medical University

Principal Investigator

SANO HAJIME  兵庫医科大学, 医学部, 教授 (00196304)

Co-Investigator(Kenkyū-buntansha) 岩崎 剛  兵庫医療大学, 薬学部, 教授 (10151721)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords関節リウマチ / IL-2 免疫複合体 / 制御性T細胞 / IL-10 / Th1 / Th17 / CIAマウス / コラーゲン関節炎 / Treg / IL-2免疫複合体 / IFN-γ / IL-17 / S1P受容体 / FTY720 / IL-2 / S1P 受容体 / SKGマウス
Outline of Final Research Achievements

To determine the effect of IL-2IC on established CIA, IL-2IC was administered for 3days from day 21 to day 23 after first immunization of CIA. To define effect of IL-2 IC on early stages of diseaseas induction we administratedIL-2IC from day 0-2 after immunization. We observed a significant decrease in both the induction the incidence and severity of arthritis in CIA mice.
Injection of IL-2IC effectively elicited more than 2-fold expansion of CD4+CD25+Foxp3+ Tregs in peripheral blood cells than control mice. Th1 and Th17 cellls infiltrations in the synovium were significantly inhibited by IL-2IC treatment. Intracellular cytokine staining revealed that IL-10 production by CD4+ cells in IL-2IC treated spleen increased four folds than in controls, and IFN-γproducing helper T cells (Th1) and Th17 producing helper T cells (Th17) were significantly decreased. Thease observations induces thatIL-2IC not only induce Tregs, but also augments Treg function by enhancing IL-10 production .

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (10 results)

All 2017 2016 2015

All Presentation (10 results) (of which Int'l Joint Research: 3 results)

  • [Presentation] 抗IL-2抗体免疫複合体によるモデルマウス関節炎抑制と制御性T細胞増強効果の検討2017

    • Author(s)
      横山 雄一,岩崎 剛,北野 幸恵 ,古川 哲也,松井 聖,佐野 統
    • Organizer
      第61回日本リウマチ学会 総会・学術集会
    • Place of Presentation
      福岡国際会議場、福岡市、福岡県
    • Year and Date
      2017-04-20
    • Related Report
      2016 Research-status Report
  • [Presentation] IC-2IC suppreses CIA in mice by the Th1/Th17 immune responses due to enhancement of both Treg numbers and Tre functions.2017

    • Author(s)
      Yokoyama Y, Iwasaki T, Kitano S, Furukawa T, Satake A, Matsui K, Sano H.
    • Organizer
      The Annual Europian Congerss of Rheumatology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] IL-2-抗IL-2抗体免疫複合体によるモデルマウス関節炎抑制と抑制性T細胞増強効果の検討2017

    • Author(s)
      横山雄一, 岩崎 剛, 北野幸恵, 古川哲也, 松井 聖, 佐野 統.
    • Organizer
      第61回日本リウマチ学会総会・学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 抗IL-2抗体複合体による関節炎モデル理療のメカニズム2017

    • Author(s)
      横山雄一, 岩崎 剛, 北野幸恵, 古川哲也, 松井 聖, 佐野 統.
    • Organizer
      第38回日本炎症・再生医学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] INVOLVEMENT OF REGULATORY T CELLS AND MICRORNAS IN REGULATION OF COLLAGEN-INDUCED ARTHRITIS IN MICE TREATED WITH IL-2/ANTI-IL-2 IMMUNE COMPLEXES.2016

    • Author(s)
      Y.Yokoyama T. Iwasaki, A. Satake, S. Shibasaki, M. Karasaki, N. Moriya, S. Kitano, K. Matsui, H. Sano.
    • Organizer
      Annual European Congress of Rheumatology
    • Place of Presentation
      ローマ、イタリア
    • Year and Date
      2016-06-09
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] PARADOXICAL EFFECTS OF INTERLEUKIN-2/ANTI-INTERLEUKIN-2 MONOCLONAL ANTIBODY IMMUNE COMPLEX ON COLLAGEN-INDUCED ARTHRITIS2016

    • Author(s)
      Y. Yokoyama, T. Iwasaki, S. Kitano, T. Furukawa, A. Satake, K. Matsui, H. Sano.
    • Organizer
      Annual European Congress of Rheumatology
    • Place of Presentation
      ロンドン、イギリス
    • Year and Date
      2016-06-08
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 抗IL-2抗体免疫複合体による関節リウマチ治療の検討2016

    • Author(s)
      横山 雄一,岩崎 剛、北野 幸恵 、古川 哲也、松井 聖、佐野 統
    • Organizer
      第60回日本リウマチ学会 総会・学術集会
    • Place of Presentation
      パシフィコ横浜、横浜市、神奈川県
    • Year and Date
      2016-04-21
    • Related Report
      2016 Research-status Report
  • [Presentation] IL-2-抗IL-2抗体免疫複合体による関節リウマチ治療の検討2016

    • Author(s)
      横山 雄一、岩崎 剛、北野 幸恵 、古川 哲也、松井 聖、佐野 統
    • Organizer
      第60回日本リウマチ学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県、横浜市)
    • Year and Date
      2016-04-21
    • Related Report
      2015 Research-status Report
  • [Presentation] IL-2-抗IL-2抗体免疫複合体による関節リウマチの治療2015

    • Author(s)
      横山 雄一、岩崎 剛、北野 幸恵、古川 哲也、関口 昌弘、東 直人、北野 将康、角田 慎一郎、松井 聖、佐野 統
    • Organizer
      第80回日本インターフェロン・サイトカイン学会
    • Place of Presentation
      東京工業大学(東京)
    • Year and Date
      2015-07-17
    • Related Report
      2015 Research-status Report
  • [Presentation] PARADOXICAL EFFECTS OF INTERLEUKIN-2/ANTI-INTERLEUKIN-2 MONOCLONAL ANTIBODY IMMUNE COMPLEX ON COLLAGEN-INDUCED ARTHRITIS2015

    • Author(s)
      T. Iwasaki , Y. Yokoyama, S. Kitano, A. Satake, K. Matsui, H. Sano
    • Organizer
      第16回欧州リウマチ学会議
    • Place of Presentation
      ローマ、イタリア
    • Year and Date
      2015-06-10
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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