Immune regulation by controlling vesicular functions in dendritic cells

• Project/Area Number: 22590434
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Kyoto University
• Principal Investigator: KADOWAKI Norimitsu 京都大学, 医学研究科, 准教授 (60324620)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 自然免疫 / 樹状細胞 / 細胞内小胞 / 免疫制御

Research Abstract

Plasmacytoid dendritic cells (pDCs) trigger autoimmune diseases by producing a large amount of IFN-alpha in response to nucleic acid. We found that the proteasome inhibitor bortezomib and the tyrosine kinase inhibitor dasatinib suppressed the IFN-alpha production by disturbing vesicular transport of nucleic acid-sensing Toll-like receptors and that of nucleic acid ligands, respectively. We thus obtained fundamental findings to develop novel immunosuppressants targeting vesicular functions in pDCs.

Research Products

• [Journal Article] 樹状細胞 特集「自己免疫疾患・アレルギー疾患 (前篇)免疫の基礎、検査、治療」 (2013)
  • Author(s): 門脇則光
  • Journal Title: 最新医学 Volume: 68 Pages: 502-512
  • URL: http://www.pieronline.jp/content/issue/0370-8241/68031
• [Journal Article] The tyrosine kinase inhibitor dasatinib suppresses cytokine production by plasmacytoid dendritic cells by targeting endosomal transport of CpG DNA (2013)
  • Author(s): Fujita H, Kitawaki T, Sato T, Maeda T, Kamihira S, Takaori-Kondo A, Kadowaki N
  • Journal Title: Eur J Immunol Volume: 43 Issue: 1 Pages: 93-103
  • DOI: 10.1002/eji.201242699
  • Peer Reviewed
• [Journal Article] Therapy for malignancies and inflammatory disorders by modulating human dendritic cell functions (2011)
  • Author(s): 門脇則光、北脇年雄、平井麻起子
  • Journal Title: Rinsho Ketsueki Volume: 52 Issue: 7 Pages: 497-504
  • DOI: 10.11406/rinketsu.52.497
  • NAID: 130004501564
  • ISSN: 0485-1439, 1882-0824
• [Journal Article] Bortezomib suppresses function and survival of plasmacytoid dendritic cells by targeting intracellular trafficking of Tol l-like receptors and endoplasmic reticulum homeostasis (2011)
  • Author(s): Hirai M, Kadowaki N, Kitawaki T, Fujita H, Takaori-Kondo A, Fukui R,Miyake K, Maeda T, Kamihira S, Miyachi Y, Uchiyama T
  • Journal Title: Blood Volume: 117 Issue: 2 Pages: 500-509
  • DOI: 10.1182/blood-2010-05-284737
  • Peer Reviewed
• [Journal Article] Bortezomib suppresses function and survival of plasmacytoid dendritic cells by targeting intracellular trafficking of Toll-like receptors and endoplasmic reticulum homeostasis (2011)
  • Author(s): Hirai M, at al
  • Journal Title: Blood Volume: 117 Pages: 500-509
  • Peer Reviewed
• [Journal Article] Optimal stimulation for CD70 induction on human monocyte-derived dendritic cells and the importance of CD70 in naive CD4^+ T cell differentiation (2010)
  • Author(s): Arimoto-Miyamoto K, et al
  • Journal Title: Immunology Volume: 130 Pages: 137-149
  • Peer Reviewed
• [Journal Article] AMLに対する免疫療法の現状と可能性 (2010)
  • Author(s): 北脇年雄、門脇則光
  • Journal Title: 血液・腫瘍科 Volume: 60 Pages: 454-459
• [Journal Article] 樹状細胞による細胞療法とその展開 (2010)
  • Author(s): 北脇年雄、門脇則光
  • Journal Title: 炎症と免疫 Volume: 18 Pages: 489-493
• [Presentation] 小胞機能を標的とした樹状細胞の機能制御。ワークショップ「アジュバント関連の基礎研究の最前線」 (2012)
  • Author(s): 門脇則光
  • Organizer: 第16回日本がん免疫学会総会
  • Place of Presentation: 札幌
• [Presentation] ABLキナーゼ阻害薬ダサチニブによるヒト形質細胞様樹状細胞の機能抑制。 (2011)
  • Author(s): 藤田晴之
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉
• [Presentation] Dasatinib potently suppresses immunostimulatory activity of human plasmacytoid dendritic cells. (2011)
  • Author(s): 藤田晴之
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] ABLキナーゼ阻害薬ダサチニブによるヒト形質細胞様樹状細胞の機能抑制。 (2011)
  • Author(s): 藤田晴之
  • Organizer: 第15回日本がん免疫学会総会
  • Place of Presentation: 豊中
• [Presentation] ABLキナーゼ阻害薬ダサチニブによるヒト形質細胞様樹状細胞の機能抑制 (2011)
  • Author(s): 藤田晴之
  • Organizer: 第15回日本がん免疫学会総会
  • Place of Presentation: 豊中
• [Presentation] Dasatinib potently suppresses immunostimulatory activity of human plasmacytoid dendritic cells (2011)
  • Author(s): 藤田晴之
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] ABLキナーゼ阻害薬ダサチニブによるヒト形質細胞様樹状細胞の機能抑制 (2011)
  • Author(s): 藤田晴之
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉
• [Presentation] Protein kinase inhibitor dasatinib potently suppresses immunostimulatory activity of human plasmacytoid dendritic cells (2010)
  • Author(s): Fujita H
  • Organizer: 52nd Annual Meeting of The American Society of Hematology
  • Place of Presentation: Orlando, USA
• [Presentation] A proteasome inhibitor bortezomib suppresses immunostimulatory activity of human plasmacytoid dendritic cells by targeting intracellular trafficking of nucleic acid-sensing Toll-like receptors and endoplasmic reticulum homeostasis (2010)
  • Author(s): Hirai M
  • Organizer: 11th International Symposium on Dendritic Cells in Fundamental and Clinical Immunology
  • Place of Presentation: Lugano, Switzerland
• [Presentation] Therapy for leukemia and inflammation through modulating human dendritic cell functions. Symposium 2: Novel approach toward dendritic cell therapy (2010)
  • Author(s): Kadowaki N
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
• [Presentation] A proteasome inhibitor bortezomib suppresses immunostimulatory activity of human plasmacytoid dendritic cells by targeting intracellular trafficking of Tol l-like receptor 9 and endoplasmic reticulum homeostasis. (2010)
  • Author(s): Hirai M, Kadowaki N, Kitawaki T, Takaori-Kondo A, Fukui R, Miyake K, Maeda T, Kamihira S, Miyachi Y, Uchiyama T
  • Organizer: 14thInternational Congress of Immunology
  • Place of Presentation: Kobe, Japan
• [Presentation] ABLキナーゼ阻害薬ダサチニブによるヒト形質細胞様樹状細胞の機能制御。 (2010)
  • Author(s): 藤田晴之
  • Organizer: 第14回日本がん免疫学会総会
  • Place of Presentation: 熊本
• [Presentation] ABLキナーゼ阻害薬ダサチニブによるヒト形質細胞様樹状細胞の機能制御 (2010)
  • Author(s): 藤田晴之, 他
  • Organizer: 第14回日本がん免疫学会総会
  • Place of Presentation: KKRホテル熊本(熊本市)
• [Presentation] Phase I/IIa clinical trials of dendritic cell-based immunotherapy for acutemyeloid leukemia in elderly patients (2010)
  • Author(s): Kitawaki T, at al
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸コンベンションセンター(神戸市)
• [Presentation] A proteasome inhibitor bortezomib suppresses immunostimulatory activity of human plasmacytoid dendritic cells by targeting intracellular trafficking of Toll-like receptor 9 and endoplasmic reticulum homeostasis (2010)
  • Author(s): Hirai M, at al
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸コンベンションセンター(神戸市)
• [Presentation] Therapy for leukemia and inflammation through modulating human dendritic cell functions Symposium 2 : Novel approach toward dendritic cell therapy (2010)
  • Author(s): Kadowaki N
  • Organizer: 第72回日本血液学会学術集会)
  • Place of Presentation: パシフィコ横浜(横浜市)(招待講演)
• [Presentation] Phase I/IIa clinical trials of dendritic cell-based immunotherapy fro acute myeloid leukemia in elderly patients using autologous apototic leukemic cells or a modified WT1 peptide as antigens (2010)
  • Author(s): Kitawaki T, et al
  • Organizer: 11th International Symposium on Dendritic Cells in Fundamental and Clinical Immunology
  • Place of Presentation: Lugano, Switzerland
• [Presentation] A proteasome inhibitor bortezomib suppresses immunostimulatory activity of human plasmacytoid dendritic cells by targeting intracellular traffickin of nucleic acid-sensing Toll-like receptors and endoplasmic reticulum homeostasis (2010)
  • Author(s): Hirai M, at al
  • Organizer: 11th International Symposium on Dendritic Cells in Fundamental and Clinical Immunology
  • Place of Presentation: Lugano, Switzerland
• [Presentation] Phase I/IIa clinical trials of dendritic cell-based immunotherapy for acute myeloid leukemia in elderly patients. (2010)
  • Author(s): Kitawaki T, at al
  • Organizer: The 1st ISCT Asia-Pacific Regional Meeting
  • Place of Presentation: フェニックスシーガイアリゾート(宮崎市)
• [Book] 血液疾患 最新の治療2011-2013 細胞療法 (2010)
  • Author(s): 門脇則光
  • Publisher: 南江堂
• [Book] がん免疫療法-実用化へのチャレンジ-、第5章 樹状細胞ワクチン (2010)
  • Author(s): 北脇年雄、門脇則光
  • Publisher: シーエムシー出版
• [Remarks]
  • URL: http://www.kuhp.kyoto-u.ac.jp/~hemonc/
• [Remarks] 京都大学大学院医学研究科 血液・腫瘍内科学
  • URL: http://www.kuhp.kyoto-u.ac.jp/~hemonc/
• [Remarks] 京都大学大学院医学研究科 血液・腫瘍内科学
  • URL: http://www.kuhp.kyoto-u.ac.jp/~hemonc/
• [Remarks]
  • URL: http://www.kuhp.kyoto-u.ac.jp/~hemonc/