Development of immunotherapy using shRNA transduced dendritic cells in bronchial asthma model

• Project/Area Number: 15K09547
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Niigata University
• Principal Investigator: KOYA TOSHIYUKI 新潟大学, 医歯学系, 准教授 (90444158)
• Co-Investigator(Kenkyū-buntansha): 坂上 拓郎 新潟大学, 医歯学総合病院, その他 (00444159) ; 長谷川 隆志 新潟大学, 医歯学総合病院, 准教授 (90361906)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 樹状細胞 / shRNA / 喘息 / 骨髄樹状細胞 / 遺伝子導入 / 喘息モデル / アレルギー喘息 / 免疫療法

Outline of Final Research Achievements

The efficiency of introducing shRNA into bone marrow-derived dendritic cells was extremely poor, and shRNA was introduced using DC 2.4 which is a cell line of dendritic cells. Introduction efficiency was low but better than bone marrow derived dendritic cells. Furthermore, the antigen presenting ability of DC 2.4 was analyzed in vitro, however, activation of T cells and elevation of cytokine production were not observed.
We attempted to prepare an asthma model using antigen - stimulated DC 2.4, but no increase in airway hyperresponsiveness to methacholine, eosinophilic airway inflammation, and elevation of type 2 cytokine in BALF were observed.
From the above, it is concluded that it is difficult to prove the hypothesis in this experimental system.

Research Products

• [Journal Article] Effects of sublingual immunotherapy in a murine asthma model sensitized by intranasal administration of house dust mite extracts (2017)
  • Author(s): Shima K, Koya T, Tsukioka K, Sakagami T, Hasegawa T, Fukano C, Ohashi-Doi K, Watanabe S, Suzuki E, Kikuchi T.
  • Journal Title: Allergology International Volume: 66 Issue: 1 Pages: 89-96
  • DOI: 10.1016/j.alit.2016.05.012
  • NAID: 130005308448
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Int'l Joint Research