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A novel therapy for allergic rhinitis using dendritic cells transfected with siRNA

Research Project

Project/Area Number 21592177
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionNagoya City University

Principal Investigator

SUZUKI Motohiko  名古屋市立大学, 大学院・医学研究科, 准教授 (50326138)

Co-Investigator(Kenkyū-buntansha) HIDA Hideki  名古屋市立大学, 大学院・医学研究科, 教授 (00305525)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2009: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords鼻科学 / アレルギー / siRNA / RNA干渉 / 樹状細胞 / CD40
Research Abstract

We previously reported that systemic administration of CD40 siRNA attenuated allergic symptoms. However, this is an allergen-nonspecific fashion. Therefore, we tried to develop a new allergen-specific therapy for allergy using CD40-silenced and allergen-pulsed dendritic cells(DCs). Bone marrow-derived DCs were transfected with CD40 siRNA and pulsed with ovalbumin(OVA). Mice were sensitized intraperitoneally with OVA and keyhole limpet hemocyanin, followed by intranasal challenge with these allergens. Mice were treated with CD40-silenced and OVA-pulsed DCs(CD40-silenced OVA DCs) before allergic sensitization. The mice receiving CD40-silenced OVA DCs inhibited allergic symptoms caused by OVA challenge, as well as anti-OVA IgE levels in sera. Also, CD40-silenced OVA DCs suppressed eosinophil infiltration at the nasal septum, OVA-specific T-cell responses, and T-cell production of IL-4 and IL-5 after stimulation with OVA. However, CD40-silenced OVA DCs did not inhibit keyhole limpet hemocyanin-induced allergy, suggesting that CD40-silenced OVA DCs induce allergen-specific tolerance. I reported that dendritic cells, which were transfected with CD40 siRNA and pulsed with ovalbumin(OVA), inhibited allergic rhinitis induced by OVA antigen but not the other antigens, suggesting that this is antigen-specific therapy.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (19 results)

All 2012 2011 2010 2009

All Journal Article (11 results) (of which Peer Reviewed: 3 results) Presentation (8 results)

  • [Journal Article] Facial nerve axotomy promotes activation of NF-kB in rat facial nucleus2011

    • Author(s)
      Safwata M, Inagakia A, Zineldeenb D, Suzuki M, Esaki S, Murakamia S
    • Journal Title

      Nagoya Med J

      Volume: 52 Pages: 25-38

    • Related Report
      2011 Final Research Report
  • [Journal Article] Intranasal therapy with CpG DNA alone for the control of allergic rhinitis2011

    • Author(s)
      Suzuki M
    • Journal Title

      Adv Otorhinolaryngol

      Volume: 72 Issue: 6 Pages: 113-115

    • DOI

      10.1586/eop.11.66

    • Related Report
      2011 Annual Research Report
  • [Journal Article] A novel allergen-specific therapy for allergy using CD40-silenced dendritic cells2010

    • Author(s)
      Suzuki M, Zheng X, Zhang X, Zhang Z, Ichim TE, Sun H, Nakamura Y, Beduhn M, Shunnar A, Garcia B, Min WP
    • Journal Title

      J Allergy Clin Immunol

      Volume: 125 Pages: 737-743

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Journal Article] RNAi-mediated CD40-CD154 interruption promotes tolerance in autoimmune arthritis2010

    • Author(s)
      Zheng X, Suzuki M, Zhang X, Ichim TE, Zhu F, Ling H, Shunnar A, Wang MH, Garcia B, Inman RD, Min W
    • Journal Title

      Arthritis Res Ther

      Volume: 12

    • Related Report
      2011 Final Research Report
  • [Journal Article] Treatment of Autoimmune Arthritis Using RNA Interference-Modulated Dendritic Cells2010

    • Author(s)
      Zheng X, Suzuki M, Ichim TE, Zhang X, Sun H, Zhu F, Shunnar A, Garcia B, Inman RD, Min W
    • Journal Title

      J Immunol

      Volume: 184 Pages: 6457-6464

    • Related Report
      2011 Final Research Report
  • [Journal Article] CD40 siRNAを導入した樹状細胞によるアレルギー性鼻炎の制御2010

    • Author(s)
      鈴木元彦、横田誠、川口仁、中村善久
    • Journal Title

      耳鼻咽喉科免疫アレルギー

      Volume: 28 Pages: 223-228

    • NAID

      10029062304

    • Related Report
      2011 Final Research Report
  • [Journal Article] 免疫療法の展望と将来-CpG DNAとsiRNAを用いた治療法を中心に-2010

    • Author(s)
      鈴木元彦
    • Journal Title

      東海花粉症研究会誌

      Volume: 21 Pages: 81-88

    • Related Report
      2011 Final Research Report
  • [Journal Article] Regulation of allery with RNA interference2009

    • Author(s)
      Suzuki M, Zheng X, Zhang X, Zhang Y, Ichim TE, Min W
    • Journal Title

      Crit Rev Immunol

      Volume: 29 Pages: 443-468

    • Related Report
      2011 Final Research Report
  • [Journal Article] Inhibition of allergic responses by CD40 gene silencing2009

    • Author(s)
      Suzuki M
    • Journal Title

      Allergy 64

      Pages: 387-397

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oligonucleotide based-strategies for allergy with special reference to siRNA2009

    • Author(s)
      Suzuki M
    • Journal Title

      Expert Opinion Biol Ther 9(4)

      Pages: 441-450

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel in vivio siRNA delivery system specifically targeting dendritic cells and silencing CD40 genes for immunomodulation2009

    • Author(s)
      Suzuki M
    • Journal Title

      Blood 113(12)

      Pages: 2646-2654

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] アレルギー性鼻炎発症後におけるsiRNA導入樹状細胞の治療効果2012

    • Author(s)
      鈴木元彦, 他
    • Organizer
      第30回日本耳鼻咽喉科免疫アレルギー学会
    • Place of Presentation
      大津
    • Year and Date
      2012-02-17
    • Related Report
      2011 Final Research Report
  • [Presentation] A novel antigen-specific therapy for allergic rhinitis with siRNA-Transfected dendritic cells2011

    • Author(s)
      Motohiko Suzuki
    • Organizer
      30th International Symposium on Infection and Allegy of the Nose
    • Place of Presentation
      ANAインターコンチネンタルホテル(東京)
    • Year and Date
      2011-09-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] A novel antigen-specific therapy for allergic rhinitis with siRNA-Transfected dendritic cells2011

    • Author(s)
      Suzuki M, Nakamura Y, Yokota A, Ohashi T, Murakami S
    • Organizer
      30th International Symposium on Infection and Allegy of the Nose
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] Int ranasal CpG DNA therapy during allergen exposure in allergic rhinitis2011

    • Author(s)
      Nakamura Y, Suzuki M, Murakami S
    • Organizer
      30th In ternational Symposium on Infection and Allegy of the Nose
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] A novel allergen-specific therapy for allergic rhinitis using CD4 0-silenced dendritic cells2010

    • Author(s)
      鈴木元彦, 他
    • Organizer
      第49回日本鼻科学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2010-08-28
    • Related Report
      2011 Final Research Report
  • [Presentation] Inhitibion of allergic responses by CD40-silenced and allergen-pulsed dendritic cells2010

    • Author(s)
      Motohiko Suzuki
    • Organizer
      14th International Congress of Immunology
    • Place of Presentation
      神戸ポートピアホテル・神戸国際展示場(兵庫県)
    • Year and Date
      2010-08-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] siRNAを用いたアレルギー性鼻炎の治療2010

    • Author(s)
      鈴木元彦
    • Organizer
      第28回日本耳鼻咽喉科免疫アレルギー学会
    • Place of Presentation
      AOSSA(福井県)
    • Year and Date
      2010-02-18
    • Related Report
      2009 Annual Research Report
  • [Presentation] Inhitibion of al lergic responses by CD40-silenced and a llergen-pulsed dendritic cells2010

    • Author(s)
      Suzuki M, Zheng X, Zhang X, Nakamura Y, Murakami S, Min WP
    • Organizer
      14th In ternational Congress of Immunology
    • Place of Presentation
      神戸
    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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