ACTIVATION MECHANISM OF INNATE IMMUNE SYSTEM BY INTERLEUKIN-15

• Project/Area Number: 19390136
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Akita University
• Principal Investigator: OHTEKI Toshiaki Akita University, 医学部, 教授 (50233200)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000); Fiscal Year 2008: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2007: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
• Keywords: 自然免疫 / 樹状細胞 / サイトカイン / Toll様受容体 / 免疫賦活 / CpG / IRF3 / IL-12 / 二量体 / 核内移行 / TLR / TLRリガンド / IRF-3

Research Abstract

インターロイキン15(IL-15)は自然免疫系の活性化に重要なサイトカインである。樹状細胞(DC)やマクロファージなどの抗原提示細胞、さらには上皮細胞などがIL-15を生産するが、その分子機構には不明な点が多い。我々は、代表的なToll様受容体リガンドであるCpGでDCを刺激すると、IL-12が生産され、IL-12依存性に転写因子IRF3が活性化して、IRF3依存性にIL-15の生産が誘導される経路を明らかにした。

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] MHC-matched corneal allograft rejection in an IFN-γ/IL-17- independent manner in C57BL/6 mice. Invest (2009)
  • Author(s): Yamada, J., Hamuro, J., Fukushima, A., Ohteki, T., Terai, K., Iwakura, Y., Yagita, H., and Kinoshita, S.
  • Journal Title: Ophth. Vis. Sci. 50 Pages: 2139-2146
  • Peer Reviewed
• [Journal Article] IL-15 serves as a costimulator in determining the activity of autoreactive CD8 T cells in an experimental mouse model of graft-versus-host-like disease (2009)
  • Author(s): Miyagawa, F., Tagaya, Y., Kim, B.S., Patel, H.J., Ishida, K., Ohteki Waldmann, T.A., and Katz, S.I.
  • Journal Title: J. Immunol. 181 Pages: 1109-1119
  • Peer Reviewed
• [Journal Article] IRF-2 protects quiescent HSCs from type-I interferon-dependent exhaustion (2009)
  • Author(s): Sato, T
  • Journal Title: Nature Medicine (in press)
  • Peer Reviewed
• [Journal Article] MRC-matched corneal allograft rejection in an IFN-gamma/IL-17-independent manner in C57BL/6 mice (2009)
  • Author(s): Yamada, J
  • Journal Title: Invest. Ophth. Vis. Sci 50 Pages: 2139-2146
  • 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] Regulatory T cells control dendritic cell/NK cell cross-talk in lymph nodes at the steady state by inhibiting CD4^+ self-reactive T cells (2008)
  • Author(s): Terme, M., Chaput, N., Combadiere, B., Ma, A., Ohteki, T., and Zitvogel, L
  • Journal Title: J. Immunol. 180 Pages: 4679-4686
  • Peer Reviewed
• [Journal Article] IL-15 serves as a costimulator in determining the activity of aUtoreactive CD8 T cells in an experimental mouse model of graft-versus-host-like disease (2008)
  • Author(s): Miyagawa, F
  • Journal Title: J. Immunol 181 Pages: 1109-1119
  • 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] Regulatory T cells control dendritic cell/NK cell cross-talk in lymph nodes at the steady state by inhibiting CD4^+ self-reactive T cells (2008)
  • Author(s): Terme, M
  • Journal Title: J. Immunol 180 Pages: 4679-4686
  • Peer Reviewed
• [Journal Article] 樹状細胞による盛分化制御 (2008)
  • Author(s): 小内伸幸
  • Journal Title: 分子細胞治療 7 Pages: 58-66
• [Journal Article] 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パイエル板樹状細胞 (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: 271-273
• [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] Regulatory T Cells Control Dendritic Cell/NK Cell Cross-Talk in Lymph Nodes at the Steady State by Inhibiting CD4+Self-Reactive T Cells. (2008)
  • Author(s): Terme, M.
  • Journal Title: J. Immunol. 180 Pages: 4679-4686
  • Peer Reviewed
• [Journal Article] Identification of clonogenic common Flt3^+MCSFR^+plasmacytoid and dendritic cell progenitors in mouse bone marrow (2007)
  • Author(s): Onai, N., Obata-Onai, A., Schmid, M.A., Ohteki, T., Jarrossay, D., and Manz, M.G.
  • Journal Title: Nat. Immunol. 8 Pages: 1207-1216
  • Peer Reviewed
• [Journal Article] 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] The Pten/PI3K pathway governs the homeostasis of Valpha14iNKT cells (2007)
  • Author(s): Kishimoto, H.,*Ohteki, T.*(*equal contribution)Yajima, N., Kawahara, K., Natsui, M., Kawarasaki, S., Hamada, K., Horie, Y., Kubo, Y., Arase, S., Taniguchi, M., Vanhaesebroeck, B., Mak, T.W., Nakano, N., Koyasu, S., Sasaki, T., and Suzuki, A.
  • Journal Title: Blood 109 Pages: 3316-3324
  • Peer Reviewed
• [Journal Article] The dynamics of dendritic cellmediated innate immune regulation (2007)
  • Author(s): Ohteki, T.
  • Journal Title: Allergol. Int 56 Pages: 209-214
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] The Pten/PI3K pathway governs the homeostasis of Valpha14iNKT cells. (2007)
  • Author(s): Kishimoto, H., Ohteki, T. (equal contribution)
  • Journal Title: Blood 109 Pages: 3316-3324
  • Peer Reviewed
• [Journal Article] The dynamics of dendritic cell-mediated innate immune regulation. (2007)
  • Author(s): Ohteki, T.
  • Journal Title: Allergy International 56 Pages: 209-214
  • NAID: 10019815295
  • Peer Reviewed
• [Presentation] Mechanisms of IgA production in the mucosa-associated lymphoid tissue (2009)
  • Author(s): 樗木俊聡
  • Organizer: 第3回JSI-RCAI免疫ワークショップ「粘膜免疫機構の制御と破綻-粘膜免疫における基礎と臨床の対話-」(招待講演)
  • Place of Presentation: 横浜
  • Year and Date: 2009-03-14
• [Presentation] Regulation of IgA production by natural ly occurring TNF/iNOS-pieducing dendritic cells (2009)
  • Author(s): Tezuka, H
  • Organizer: The 4th Stage Surface Barrier Immunology Study Group (SBARIS) 1st Meeting 「Immune Response at Mucosal Surface」
  • Place of Presentation: Tokyo
  • Year and Date: 2009-03-06
• [Presentation] Proliferation and exhausion of HSCs by type-1 interferon (2009)
  • Author(s): Ohteki, T.
  • Organizer: 第8回日本再生医療学会総会, シンポジウムStem Cell Niche
  • Place of Presentation: 東京
• [Presentation] Regulation of mucosal IgA production by dendritic cells (2009)
  • Author(s): Ohteki, T
  • Organizer: The 2^<nd> International Symposium of WPI-IFReC "Dynamids of Immune Responses"(招待講演)
  • Place of Presentation: Osaka, Japan
• [Presentation] Proliferation and exhausion of HSCs by type-1 interferon (2009)
  • Author(s): Ohteki, T
  • Organizer: 第8回日本再生医療学会総会, シンポジウムStem Cell Niche(招待講演)
  • Place of Presentation: 東京
• [Presentation] The role of hematopoietic cytokine in dendritic cell subsets development (2008)
  • Author(s): Onai, N.
  • Organizer: 第38日本免疫学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] IRF-2 protects haematopoietic stem cells from type-I interferon-dependent replicative exhaustion (2008)
  • Author(s): Sato, T.
  • Organizer: 第38日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] Molecular mechanism of IL-15 production from DC upon CpG stimulation in vivo (2008)
  • Author(s): Kuwajima, S.
  • Organizer: 第38日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] Molecular mechanism of DC production of IL-15 upon CpG stimulation in vivo (2008)
  • Author(s): Fujioka, Y.
  • Organizer: The 10th International Symposium on Dendritic Cells
  • Place of Presentation: 神戸
• [Presentation] Critical roles for Nod-like receptor in dendritic cell-mediated cross-priming induction in vivo (2008)
  • Author(s): Asanci, J
  • Organizer: The 8th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Awaji, Japan
• [Presentation] Regulation of mucosal IgA production by dendritec cell (2008)
  • Author(s): Ohteki, T
  • 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] Molecular mechanism of DC production of IL-15 upon CpG stimulation in vivo (2008)
  • Author(s): Fujioka, Y
  • 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 dell-independent IgA production (2008)
  • Author(s): Teaka, H
  • Organizer: 第38日本免疫学会学術集会
  • Place of Presentation: 京都
• [Presentation] IRF-2 protects haematopoietic stem cells from type-I interferon-dependen renlicative 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] 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] Molecularmechanism of IL-15 production from DC upon CpG stimulation in vivo (2008)
  • Author(s): Kuwajima, S
  • Organizer: 第38日本免疫学会学術集会
  • Place of Presentation: 京都
• [Presentation] 腸管粘膜組織におけるIgA生産調節機構 (2008)
  • Author(s): 樗木俊聡
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会シンポジウム「血球細胞の分化系譜」招待講演)
  • Place of Presentation: 神戸
• [Presentation] Nucleotide-bihding oligomerization domain(Nod)シグナルによるDCクロスプライミングの増強効果 (2008)
  • Author(s): 浅野純平
  • Organizer: 第18回Kyoto T Cell Cohference
  • Place of Presentation: 京都
• [Presentation] 粘膜免疫系を支配するガス (2008)
  • Author(s): 樗木俊聡
  • Organizer: 第32回阿蘇シンポジウム(招待講演)
  • Place of Presentation: 阿蘇
• [Presentation] 樹状細胞による免疫調節ダイナミズム研究 (2007)
  • Author(s): 樗木俊聡
  • Organizer: 第10回日本免疫学会賞受賞講演)第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-21
• [Presentation] pDC-derived interferon-α downregulates TLR7-mediated immune responses through DC apoptosis (2007)
  • Author(s): Kuwajima, S.
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-21
• [Presentation] 樹状細胞による免疫調節ダイナミズム研究 (2007)
  • Author(s): 樗木俊聡
  • Organizer: 第37回日本免疫学会第10回日本免疫学会賞受賞者講演
  • 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] 樹状細胞による粘膜免疫調節機構 (2007)
  • Author(s): 樗木俊聡
  • Organizer: 第3回東北内分泌研究会総会(第15回日本内分泌学会東北地方会)
  • Place of Presentation: 秋田
  • Year and Date: 2007-10-13
• [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] Plasmacytoid dendritic cell-derived interferon-α regulates dendritic cell homeostasis (2007)
  • Author(s): Kuwajima, S.
  • 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] 形質細胞様樹状細胞の生産するIFN-αによる新規免疫制御機構 (2007)
  • Author(s): 樗木俊聡
  • Organizer: 第18回樹状細胞研究会
  • Place of Presentation: 淡路
• [Presentation] Plasmacytoid dendritic cell-derived interferon-a regulates dendritic cell homeostasis (2007)
  • Author(s): Ohteki, T.
  • Organizer: International Symposium on Molecular Cell Biology of Macrophages 2007
  • Place of Presentation: 静岡
• [Presentation] Plasmacytoid dendritic cell-derived interferon-α regulates dendritic cell homeostasis. (2007)
  • Author(s): Ohteki, T.
  • Organizer: International Symposium on Molecular Cell Biology of Macrophages 2007
  • Place of Presentation: 静岡
• [Presentation] Regulation of IgA production by naturally occurring TNF/iNOS-producing dendritic cells. (2007)
  • Author(s): Ohteki, T.
  • Organizer: The Korean Association of Immunobiologies 55th Fall Conference
  • Place of Presentation: ソウル(韓国)
• [Presentation] 形質細胞様樹状細胞の生産するIFN-αによる新規免疫制御機構. (2007)
  • Author(s): 樗木俊聡
  • Organizer: 第18回樹状細胞研究会
  • Place of Presentation: 淡路
• [Presentation] Plasmacytoid dendritic cell-derived interferon-α regulates dendritic cell homeostasis. (2007)
  • Author(s): Kuwajima, S.
  • Organizer: 第7回あわじしま感染症・免疫フォーラム
  • Place of Presentation: 淡路
• [Book] 樹状細胞による免疫調節ダイナミズム,免疫応答と免疫病態の統合的分子理解(谷口維紹, 本一彦) (2007)
  • Author(s): 樗木俊聡
  • Publisher: 南山堂,東京
• [Book] CpGによる樹状細胞活性化とIL-15 依存性クロストーク. Annual Review免疫2008(奥村康, 平野俊夫, 佐藤昇志) (2007)
  • Author(s): 桑島精一、樗木俊聡
  • Publisher: 中外医学社,東京
• [Book] 樹状細胞による免疫調節ダイナミズム(pp.125-134)谷口維紹、山本一彦(編)免疫応答と免疫病態の統合的分子理解 (2007)
  • Author(s): 樗木俊聡
  • Total Pages: 269
  • Publisher: 南山堂
• [Book] CpGによる樹状細胞活性化とIL-15依存性クロストーク.(pp.138-145)奥村康, 平野俊夫, 佐藤昇志(編)Annual Review免疫2008 (2007)
  • Author(s): 桑島精一
  • Total Pages: 317
  • Publisher: 中外医学社
• [Remarks]
  • URL: http://www.med.akita-u.ac.jp/~kisei/Default.html
• [Remarks]
  • URL: http://www.med.akita-u.ac.jp/~kisei/Default.html
• [Remarks]
  • URL: http://www.med.akita-u.ac.jp/~kisei/Default.html