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

2011 Fiscal Year Final Research Report

• Project/Area Number: 21592177
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Nagoya 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
• Keywords: 鼻科学

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.

Research Products

• [Journal Article] Facial nerve axotomy promotes activation of NF-kB in rat facial nucleus (2011)
  • Author(s): Safwata M, Inagakia A, Zineldeenb D, Suzuki M, Esaki S, Murakamia S
  • Journal Title: Nagoya Med J Volume: 52 Pages: 25-38
• [Journal Article] A novel allergen-specific therapy for allergy using CD40-silenced dendritic cells (2010)
  • 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
• [Journal Article] RNAi-mediated CD40-CD154 interruption promotes tolerance in autoimmune arthritis (2010)
  • 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 Pages: R13
• [Journal Article] Treatment of Autoimmune Arthritis Using RNA Interference-Modulated Dendritic Cells (2010)
  • 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
• [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
• [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
• [Journal Article] Regulation of allery with RNA interference (2009)
  • Author(s): Suzuki M, Zheng X, Zhang X, Zhang Y, Ichim TE, Min W
  • Journal Title: Crit Rev Immunol Volume: 29 Pages: 443-468
• [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
• [Presentation] A novel antigen-specific therapy for allergic rhinitis with siRNA-Transfected dendritic cells (2011)
  • 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
  • Year and Date: 20110620-24
• [Presentation] Int ranasal CpG DNA therapy during allergen exposure in allergic rhinitis (2011)
  • 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
  • Year and Date: 20110620-24
• [Presentation] Inhitibion of al lergic responses by CD40-silenced and a llergen-pulsed dendritic cells (2010)
  • 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
  • Year and Date: 20100822-27
• [Presentation] A novel allergen-specific therapy for allergic rhinitis using CD4 0-silenced dendritic cells (2010)
  • 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