Nod1-mediated regulation of immunological homeostasis

• Project/Area Number: 19590489
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Akita University
• Principal Investigator: SATO Taku (2008) Akita University, 医学部, 助教 (40375259); 多田 浩之 (2007) Akita University, 医学系研究科, 特別研究員 (70431632)
• Co-Investigator(Kenkyū-buntansha): ONAI N. Obuyuki 秋田大学, 医学部, 講師 (50323605) ; TEZUKA Hiroyuki 秋田大学, 医学部, 助教 (30375258) ; TADA Hiroyuki 秋田大学, 大学院・医学系研究科, 特別研究員 (70431632) ; 佐藤 卓 秋田大学, 医学部, 助教 (40375259)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 抗原 / NOD1 / Cross-priming / dendritic cell / Cytotoxic T lymphocyte / Endotoxin shock / Nod1 / Dendritic cell / Cytotoxic T lymphocytes

Research Abstract

本研究では、細菌由来ペプチドグリカンの細胞内センサーであるNod1を介したシグナルが、CD8α^+樹状細胞(DC)のクロスプレゼンテーション能を増強し、より効果的に抗原特異的細胞障害性T 細胞の増殖及び活性化を誘導しうることを明らかにした。他方、Nod1刺激物質を投与したマウスはエンドトキシンショックに対する感受性が高まることから、同刺激が強力なアジュバンド活性を有することが判明した。これらの結果は、これまでに知られていなかったNod1シグナルを介する防御免疫応答機構を明らかにするとともに、新たな抗腫瘍免疫治療の開発に繋がる可能性を含む重要な知見と考えられた。

Research Products

• [Journal Article] IRF-2 protects quiescent HSCs from type-I interferondependent exhaustion (2009)
  • Author(s): Sato, T., Onai, N., Yoshihara, H., Arai, F., Suda, T., and Ohteki, T.
  • Journal Title: Nat. Med. (in press)
  • Peer Reviewed
• [Journal Article] Effective clearance of intracellular Leishmania major in vivo requires Pten in macrophages (2008)
  • Author(s): Kuroda, S., Nishio, M., Sasaki, T., Horie, Y., Kawahara, K., Sasaki, M., Natsui, M., Matozaki, T., Tezuka, H., Ohteki, T., Forster, I., Mak, T.W., Nakano, T., and Suzuki, A.
  • Journal Title: Eur. J. Immunol 38 Pages: 1331-1340
  • Peer Reviewed
• [Journal Article] The STATs on dendritic cell development (2008)
  • Author(s): Onai, N. and Manz, M.G.
  • Journal Title: Immunity 28 Pages: 490-492
  • Peer Reviewed
• [Journal Article] Effective clearance of intracellular Leishmania major in vivo requires Pten in macrophages (2008)
  • Author(s): Kuroda, S.
  • Journal Title: Eur. J. Immunol. 38 Pages: 1331-1340
  • Peer Reviewed
• [Journal Article] The STATs on dendritic cell development (2008)
  • Author(s): Onai, N.
  • Journal Title: Immunity 28 Pages: 490-492
  • Peer Reviewed
• [Journal Article] 樹状細胞によるTh分化制御 (2008)
  • Author(s): 小内伸幸
  • Journal Title: 分子細胞治療 7 Pages: 58-66
• [Journal Article] 血液前駆細胞から樹状細胞サブセットへの分化経路 (2008)
  • Author(s): 小内伸幸
  • Journal Title: 実験医学増刊号 26 Pages: 3149-3157
• [Journal Article] 腸管における樹状細胞のトラフィッキングとIgA生産誘導機構 (2008)
  • Author(s): 手塚裕之
  • Journal Title: 臨床免疫・アレルギー科 49 Pages: 10-15
• [Journal Article] IgAクラススイッチを誘導するバイエル板樹状細胞 (2008)
  • Author(s): 手塚裕之
  • Journal Title: 臨床免疫・アレルギー科 50 Pages: 216-221
• [Journal Article] 腸管粘膜樹状細胞によるIgAクラススイッチ制御-腸内常在菌の役割 (2008)
  • Author(s): 手塚裕之
  • Journal Title: 医学のあゆみ 227 Pages: 326-331
• [Journal Article] 腸管でのIgA生産を司るTNF/iNOS生産性樹状細胞とその機能 (2008)
  • Author(s): 手塚裕之
  • Journal Title: 生体の科学 59 Pages: 268-274
• [Journal Article] 消化管粘膜での免疫応答における樹状細胞の役割-小腸粘膜樹状細胞によるIgAクラススイッチ制御 (2008)
  • Author(s): 手塚裕之
  • Journal Title: 実験医学 26 Pages: 3236-3242
• [Journal Article] 樹状細胞によるIgA生産誘導機構の新知見 (2008)
  • Author(s): 樗木俊聡
  • Journal Title: 炎症と免疫 16 Pages: 209-214
• [Journal Article] 粘膜樹状細胞によるIgAクラススイッチ誘導機構 (2008)
  • Author(s): 安部由紀子
  • Journal Title: 感染・炎症・免疫 38 Pages: 271-253
• [Journal Article] Effective clearance of intracellular Leishmania major in vivo requires Pten in macrophages. (2008)
  • Author(s): Kuroda, S.
  • Journal Title: Eur. J. Immunol. 38 Pages: 1331-1340
  • Peer Reviewed
• [Journal Article] Identification of clonogenic common Flt3^+MCSFR^+plasmacytoid and dendritic cell progenitors in mouse bone marrow (2007)
  • Author(s): Onai1, N., Obata-Onai1, A., Schmid, M.A., Ohteki, T., Jarrossay, D., and Manz, M.G.
  • Journal Title: Nat. Immunol 8 Pages: 1207-1216
  • Peer Reviewed
• [Journal Article] Regulation of IgA production by naturally occurring TNF/iNOSproducing dendritic cells (2007)
  • Author(s): Tezuka, H., Abe, Y., Iwata, M, Takeuchi, H., Ishikawa, H., Matsushita, M., Shiohara, T., Akira, S., and Ohteki, T.
  • Journal Title: Nature 448 Pages: 929-933
  • Peer Reviewed
• [Journal Article] Flt3 in regulation of type-I interferon producing and dendritic cell development (2007)
  • Author(s): Onai, N., Obata-Onai, A., Schmid, M., and Manz, MG.
  • Journal Title: Ann. N. Y. Acad. Sci. 1106 Pages: 253-261
  • Peer Reviewed
• [Journal Article] IL-15による炎症反応の制御 (2007)
  • Author(s): 樗木俊聡、多田浩之
  • Journal Title: 感染・炎症・免疫 27 Pages: 10-16
• [Journal Article] 樹状細胞からのIL-15生産と炎症 (2007)
  • Author(s): 多田浩之、樗木俊聡
  • Journal Title: 臨床免疫・アレルギー科 48 Pages: 340-346
  • NAID: 40015658148
• [Journal Article] Identification of clonogenic common Flt3^+M-CSFR^+ plasmacytoid and dendritic cell progenitors in mouse bone marrow. (2007)
  • Author(s): Onai, N.
  • Journal Title: Nat. Immunol. 8 Pages: 1207-1216
  • Peer Reviewed
• [Journal Article] Regulation of IgA production by naturally occurring TNF/iNOS-producing dendritic cells. (2007)
  • Author(s): Tezuka, H.
  • Journal Title: Nature 448 Pages: 929-933
  • NAID: 40016204559
  • Peer Reviewed
• [Journal Article] Flt3 in regulation of type-I interferon producing and dendritic cell development. (2007)
  • Author(s): Onai, N.
  • Journal Title: Ann. N. Y. Acad. Sci. 1106 Pages: 253-261
  • Peer Reviewed
• [Journal Article] 樹状細胞サブセットの分化経路 (2007)
  • Author(s): 小内伸幸
  • Journal Title: 生化学 79 Pages: 1143-1148
  • NAID: 10020284334
• [Journal Article] 樹状細胞によるIgAクラススイッチ誘導機構 (2007)
  • Author(s): 手塚裕之
  • Journal Title: 臨床免疫・アレルギー科 48 Pages: 230-235
• [Journal Article] 樹状細胞からのIL-15生産と炎症 (2007)
  • Author(s): 多田浩之
  • Journal Title: 臨床免疫・アレルギー科 48 Pages: 340-346
  • NAID: 40015658148
• [Journal Article] 粘膜TiP-DCによるIgA生産誘導機構. (2007)
  • Author(s): 手塚裕之
  • Journal Title: 臨床免疫・アレルギー科 47 Pages: 619-624
• [Journal Article] IL-15による炎症反応の制御. (2007)
  • Author(s): 樗木俊聡
  • Journal Title: 感染・炎症・免疫 37 Pages: 10-16
• [Presentation] Critical roles for Nod-like receptor in dendritic cell-mediated cross-priming induction in vivo (2008)
  • Author(s): Asano, J.
  • Organizer: 第38日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] Critical roles for Nod-like receptor in dendritic cell-mediated cross-priming induction in vivo (2008)
  • Author(s): Asano, J.
  • Organizer: The 10th International Symposium on Dendritic Cells
  • Place of Presentation: 神戸
• [Presentation] IRF-2 protects haematopoietic stem cells from type-I interferon-dependent replicative exhaustion (2008)
  • Author(s): Sato, T.
  • Organizer: 第38日本免疫学会学術集会
  • Place of Presentation: 京都
• [Presentation] Regulation of dendritic cell homeostasis (2008)
  • Author(s): Onai, N.
  • Organizer: The 10th international Symposium on Dendritic Cells(招待講演)
  • Place of Presentation: Kobe, Japan
• [Presentation] Critical roles for Nod-like receptor in dendritic cell-mediated cross-priming induction in vivo (2008)
  • Author(s): Asano, J.
  • Organizer: The 10th International Symposium on Dendritic Cells
  • Place of Presentation: Kobe, Japan
• [Presentation] Regulation of mucosal IgA production by dendritic cells (2008)
  • Author(s): Ohteki, T.
  • Organizer: 第38日本免疫学会学術集会Simposium 5 Dendritic cell(招待講演)
  • Place of Presentation: 京都
• [Presentation] The role of hematopoietic cytokine in dendritic cell subsets development (2008)
  • Author(s): Onai, N
  • Organizer: 第38日本免疫学会学術集会
  • Place of Presentation: 京都
• [Presentation] Critical role for pDCs in mucosal T cell-independent IgA production (2008)
  • Author(s): Teztca, H.
  • Organizer: 第38日本免疫学会学術集会
  • Place of Presentation: 京都
• [Presentation] Critical roles for Nod-like receptor in dendritic cell-mediated cross-priming induction in vivo (2008)
  • Author(s): Asano, J.
  • Organizer: 第38日本免疫学会学術集会
  • Place of Presentation: 京都
• [Presentation] Identification of clonogenic common plasmacytoid and dendritic cell progenitors in mouse bone marrow. (2007)
  • Author(s): Onai, N.
  • Organizer: 第37回日本免疫学会Late breaking symposiun
  • Place of Presentation: 東京
  • Year and Date: 2007-11-22
• [Presentation] Regulation of IgA production by naturally Occurring TNF/iNOS-producting dendritic cells. (2007)
  • Author(s): Tezuka, H.
  • Organizer: 第37回日本免疫学会Late breaking symposium
  • Place of Presentation: 東京
  • Year and Date: 2007-11-22
• [Presentation] Limited role of denderitic cells in the maintenance of memory CD8^+ Tcells in lymphoreplete host. (2007)
  • Author(s): Sato, T.
  • Organizer: 第37回日本免疫学会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-22
• [Presentation] Identification of clonogenic common plasmacytoid and dendritic cell progenitors in mouse bone marrow. (2007)
  • Author(s): Onai, N.
  • Organizer: 第37回日本免疫学会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-21
• [Presentation] Regulation of IgA production by mucosal CCL2^+ dendritic cells. (2007)
  • Author(s): Tezuka, H.
  • Organizer: 第37回日本免疫学会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-21
• [Presentation] pDC-derived interferon-α downregulatesTLR7-mediated immune responses through DC apoptosis. (2007)
  • Author(s): Kuwajima, S.
  • Organizer: 第37回日本免疫学会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-21
• [Presentation] Interleukin-15 regulates Th17 differentiation in collagen-induced arthritis. (2007)
  • Author(s): Inaba,M.
  • Organizer: 第37回日本免疫学会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-21
• [Presentation] マウス骨髄における樹状細胞前駆細胞の同定 (2007)
  • Author(s): 小内伸幸
  • Organizer: 第2回群馬大学・秋田大学連携グローバルCOEプログラム「生体調節シグナルの統合的研究」第一回若手ミニシンポジウム
  • Place of Presentation: 秋田
  • Year and Date: 2007-11-03
• [Presentation] IgA生産調節メカニズムの新知見. (2007)
  • Author(s): 樗木俊聡
  • Organizer: 歯科基礎医学会シンポジウム
  • Place of Presentation: 札幌
  • Year and Date: 2007-08-30
• [Presentation] メモリーCD8T細胞の数的・機能的維持における樹状細胞の役割 (2007)
  • Author(s): 佐藤 卓
  • Organizer: 第17回Kyoto T Cell Conference (KTCC) 2007
  • Place of Presentation: 京都
  • Year and Date: 2007-06-16
• [Presentation] TNF/iNOS生産樹状細胞によるIgA生産調節機構. (2007)
  • Author(s): 樗木俊聡
  • Organizer: 第61回日本細菌学会東北支部総会
  • Place of Presentation: 仙台
• [Presentation] Plasmacytoid dendritic cell-derived interferon-α regulates dendritic cell homeostasis. (2007)
  • Author(s): Ohteki, T.
  • Organizer: 第7回あわじしま感染症・免疫フォーラム
  • Place of Presentation: 淡路
• [Presentation] Prospective isolation of clonogenic common plasmacytoid and dendritic progenitors in mouse bone marrow. (2007)
  • Author(s): Onai, N.
  • Organizer: 第20回内藤コンファレンス「自然免役の医学・生物学(III)」
  • Place of Presentation: 葉山
• [Remarks]
  • URL: http://www.med.akita-u.ac.jp/~kisei/Default.html
• [Remarks]
  • URL: http://www.med.akita-u.ac.jp/~kisei/Default.html