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Development of second generation therapeutic strategy based on genome information

Research Project

Project/Area Number 19390278
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

KUBO Masato  The Institute of Physical and Chemical Research, シグナル・ネットワーク研究チーム, チームリーダー (40277281)

Co-Investigator(Kenkyū-buntansha) TAMARI Mayumi  独立行政法人理化学研究所, アレルギー体質関連遺伝子研究チーム, チームリーダー (00217184)
INOUE Hiromasa  九州大学大学院, 附属胸部疾患研究施設, 講師 (30264039)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2008: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2007: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Keywordsアレルギー・喘息 / シグナル伝達 / 免疫学 / IL-4 / Th1 / Th2 / 転写制御 / I型アレルギー反 / エンハンサー / サイレンサー / I型アレルギー反応
Research Abstract

花粉症、喘息、アトピー性皮膚炎などのアレルギーは、Th2と呼ばれる特殊なT細胞サブセットから主に産生されるサイトカインによって制御されている。これらサイトカイン遺伝子の多くは、同一染色体上にクラスターとして存在し、そのゲノム構造は哺乳動物間で高度に保存されることにより、遺伝情報を共有している。本研究は、タンパク質として翻訳される以外のゲノム領域にある遺伝情報に焦点を当て、その情報を明らかにすることにより、次世代に向けたアレルギー治療法の開発を目指すものである。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (54 results)

All 2009 2008 2007 Other

All Journal Article (30 results) (of which Peer Reviewed: 30 results) Presentation (13 results) Book (9 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells through targeting SOCS12009

    • Author(s)
      Lu, L-F., Thai, T-H, Dinis Pedro Calado, D.P.,Chaudhry, A., Kubo, M., Kentaro Tanaka, K. Gabriel, B. G., Lee, H., Yoshimura, A., Klaus Rajewsky, R., Alexander Y. Rudensky
    • Journal Title

      Immunity 30

      Pages: 80-91

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] BLNK suppresses pre-B cell leukemogenesis though inhibition of Jak32009

    • Author(s)
      Nakayama, J., Yamamoto, M., Hayashi, K., Satoh, H., Bundo, K., Kubo, M., Goitsuka, R., Farrar, M.A., Kitamura, D.
    • Journal Title

      Blood Feb 12;113(7)

      Pages: 1483-92

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of Th1 vs. Th17 differentiation: Selective contribution of thetranscription factor IRF1 to the IFN-・-IL-12 axis of signaling networks in CD4^+ T cells2008

    • Author(s)
      Kano, S., Sato, K., Morishita, Y., Vollstedt, S., Kim, S., Taki, S., Honda, K., Kubo, M., & Taniguchi, T.
    • Journal Title

      Nature Immunology 9(1)

      Pages: 34-41

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Murine IL-4 is able to signal via chimeric human IL-4R・/mouse ・-chain receptor2008

    • Author(s)
      Myburgh, E., Horsnell, W., Cutler, A.J., Arendse, B., Kubo, M., Brombacher, F.
    • Journal Title

      Mol. Immunol. 45(5)

      Pages: 1327-1336

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pleiotropic Roles of Runx Transcription Factors in the Differentiation and Function of T Lymphocytes2008

    • Author(s)
      Kohfu, K., Kubo, M., Ichikawa, H., Ohno, S., Habu, S., Sato, T., and Satake, M.
    • Journal Title

      Current Immunology Reviews 4

      Pages: 10-115

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of Th1 vs.Th17 differentiation:Selective contribution of the transcription factor IRF1 to the IFN-γ-IL-12 axis of signaling networks in CD4^+T cells2008

    • Author(s)
      Kano, S.
    • Journal Title

      Nature lmmunology 9

      Pages: 34-41

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Murine IL-4 is able to signal via chimeric human IL-4Rα/mouseγ-chain receptor2008

    • Author(s)
      Myburgh, E.
    • Journal Title

      Mol.Immunol 45(5)

      Pages: 1327-1336

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] T細胞サブセット:分化のメカニズムと免疫疾患の制御2008

    • Author(s)
      久保 允人
    • Journal Title

      細胞工学 27(2)

      Pages: 110-112

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Notchによるアレルギー・Th2分化制御2008

    • Author(s)
      田中 伸弥
    • Journal Title

      細胞工学 27(2)

      Pages: 132-136

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of IL-7/STAT5 pathway and suppressor of cytokine signaling 1 in maintenance of naive and memory CD4 T cells in peripheral lymphoid organs2007

    • Author(s)
      Seki, Y., Yang, J., Okamoto, M., Tanaka, S., Goizuka, Farrar, M.A., R., and Kubo, M.
    • Journal Title

      J. Immunol. 1;178(1)

      Pages: 262-70

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of endogenous inhibitors of cytokine signaling in allergic asthma2007

    • Author(s)
      Inoue, H., Fukuyama, S., Kubo, M., and Yoshimura, A.
    • Journal Title

      Current Medicinal Chemistry 14

      Pages: 181-189

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of Suppressor of Cytokine Signaling-3 in T cells Exacerbates Acetaminophen-induced Hepatotoxicity2007

    • Author(s)
      Numata, K., Kubo, M., Watanabe, H., Takagi, K., Mizuta, H., Okada, S., Ito, T., and Matsukawa, A.
    • Journal Title

      J. Immunol. 178

      Pages: 3777-3785

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of the Programmed Death-1/Programmed Death-1 Ligand Pathway in CD4-CD25- Regulatory T-Cell Activity to Suppress Alloimmune Responses2007

    • Author(s)
      Kitazawa, Y., Fujino, M., Wang, Q., Kimura, H., Azuma, M., Kubo, M., Abe, R., and Li, X-K.
    • Journal Title

      Transplantation 83

      Pages: 774-782

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] SOCS proteins, cytokine signalling and immune regulation2007

    • Author(s)
      Yoshimura, A., Naka, T., Kubo, M.
    • Journal Title

      Nature Review Immunology 7

      Pages: 454-465

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Notch: filling a hole in T helper 2 cell differentiation2007

    • Author(s)
      Kubo, M.
    • Journal Title

      Immunity 27

      Pages: 3-5

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] The regulation of Il4 gene expression in mast cells and basophils is regulated by distinct proximal and distal 3' enhancers2007

    • Author(s)
      Yagi, R., Tanaka, S., Motomura, Y., and Kubo, M.
    • Journal Title

      Mol. Cell. Biol. 27(23)

      Pages: 8087-8097

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory dendritic cells protect against cutaneous chronic graft-versus -host disease mediated through CD4^+CD25^+Foxp3^+ regulatory T cells2007

    • Author(s)
      Fujita, S., Sato, Y., Sato, K., Eizumi, K., Kubo, M. Fukaya, T., and Sato, K.
    • Journal Title

      Blood 110 (10)

      Pages: 3793-803

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Construction of an open-access database that integrates crossreference information from the transcriptome and proteome of immune cells2007

    • Author(s)
      Hijikata A, Kitamura H, Kimura Y, Yokoyama R, Aiba Y, Bao Y, Fujita S, Hase K, Hori S, Kanagawa O, Kawamoto H, Kawano K, Koseki H, Kubo M, Kurita Miki A,Kurosaki T, Masuda K, Nakata M, Oboki K, OhnoH, Okamoto M, Okayama Y, O-Wang J, Saito H, Saito T, Sakuma M, Sato K, Sato K, Seino K, Setoguchi R, Tamura Y, Tanaka M, Taniguchi M, Taniuchi I, Teng A, Watanabe T, Watarai H, Yamasaki S, Ohara O.
    • Journal Title

      Bioinformatics 23(21)

      Pages: 2934-2941

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of the Programmed Death-1/Programmed Death-1 Ligand Pathway in CD4^-CD25^- Regulatory T-Cell Activity to Suppress Alloimmune Responses2007

    • Author(s)
      Kitazawa, Y.
    • Journal Title

      Transplantation 83

      Pages: 774-782

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Notch:filling a hole in The helper 2 cell differentiation2007

    • Author(s)
      Kubo, M.
    • Journal Title

      Immunity 27

      Pages: 3-5

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The regulation of 114 gene expression in mast cells and basophils is regulated by distinct proximal and distal 3'enhancers2007

    • Author(s)
      Yagi, R.
    • Journal Title

      Mol.Cell.Biol 27(23)

      Pages: 8087-8097

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory dendritic cells protect against cutaneous chronic graft-versus-host disease mediated through CD4^+CD25^+Foxp3^+ regulatory T cells2007

    • Author(s)
      Fujita, S.
    • Journal Title

      Blood 110(10)

      Pages: 3793-3803

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Construction of an open-access database that integrates crossre ference information from the transcriptome and proteome of immune cells2007

    • Author(s)
      Hijikata, A.
    • Journal Title

      Bioinformatics 23(21)

      Pages: 2934-2941

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] メモリー型T細胞:アレルギー反応を制御する新たなT細胞サブセット2007

    • Author(s)
      久保 允人
    • Journal Title

      アレルギー・免疫 14(2)

      Pages: 12-18

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Th2細胞とマスト細胞におけるIL-4発現制御2007

    • Author(s)
      田中 伸弥
    • Journal Title

      臨床免疫 47(1)

      Pages: 26-32

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Th1/Th2応答とクロマチン制御2007

    • Author(s)
      久保 允人
    • Journal Title

      南山堂

      Pages: 77-86

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MINA53, an Il4 co-repressor controlling Th2-bias

    • Author(s)
      Okamoto, M., Van Stry, M., Chung, L., Koyanagi, M., Sun, X., Suzuki, Y., Ohara, O.,Kitamura, H., Hijikata, A., M., Bix, and Kubo, M.
    • Journal Title

      Nat. Immunol. (in press)

      Pages: 0-0

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Runx3 transcription factor promotes TH1 differentiation by interacting with and attenuating GATA3

    • Author(s)
      Kohu, K., Ohmori, H., Wen, F. W., Onda, D., Wakoh, T., Yamashita, M., Toshinori Nakayama, T., Kubo, M., and Satake, M.
    • Journal Title

      J. Immunol. (in press)

      Pages: 0-0

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Non-canonical IL-17 producing memory T cells regulate the initial phase of neutrophil mediated airway responses

    • Author(s)
      Tanaka, S., Yoshimoto, T., Naka, T., Nakae S., Iwakura Y., Cua, D. and Kubo, M.
    • Journal Title

      J. Immunol. (in press)

      Pages: 0-0

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pulmonary suppressor of cytokine signalling (SOCS)-1 induced by IL-13 as regulates allergic asthma

    • Author(s)
      Fukuyama, S., Nakano, T., Matsumoto,T., Oliver, B. G. G., Burgess, J., Moriwaki, A., Tanaka, K., Kubo, M., Hoshino, T., Tanaka, H., McKenzie, A. N. J. Matsumoto, K., Aizawa, H., Nakanishi, Y., Yoshimura, A., Black, J. L., and Inoue, H.
    • Journal Title

      Am. J. Respiratory and Critical Care Med. (in press)

      Pages: 0-0

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Presentation] 好塩基球、肥満細胞の誘導型欠損マウスの作製2008

    • Author(s)
      澤口 穣、田中 伸弥、中江 進、久保允人
    • Organizer
      第38回日本免疫学会総会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-03
    • Related Report
      2008 Final Research Report
  • [Presentation] ConA肝炎におけるT細胞SOCS3の役割解明2008

    • Author(s)
      Fushimi S, Takahata T, Wakabayashi H, Ogino T, Kubo M
    • Organizer
      第38回日本免疫学会総会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-03
    • Related Report
      2008 Final Research Report
  • [Presentation] TGF-beta1 inhibitsTh1/Th2 development through epigenetic modification of cytokine locus independent on Foxp3 expression2008

    • Author(s)
      大野慎一郎、久保允人
    • Organizer
      第38回日本免疫学会総会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-01
    • Related Report
      2008 Final Research Report
  • [Presentation] ヘルパーT細胞分化におけるサイトカイン遺伝子の時空的制御2008

    • Author(s)
      本村 泰隆、久保允人
    • Organizer
      第38回日本免疫学会総会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-01
    • Related Report
      2008 Final Research Report
  • [Presentation] E4BP4によるI型ヘルパーT細胞におけるIL-13遺伝子の発現制御2008

    • Author(s)
      本村 泰隆、久保允人
    • Organizer
      第18回京都T細胞会議
    • Place of Presentation
      京都
    • Year and Date
      2008-06-14
    • Related Report
      2008 Final Research Report
  • [Presentation] 免疫性疾患におけるCNS-2エンハンサーの重要性2008

    • Author(s)
      田中伸弥、久保允人
    • Organizer
      第18回京都T細胞会議
    • Place of Presentation
      京都
    • Year and Date
      2008-06-14
    • Related Report
      2008 Final Research Report
  • [Presentation] Runx3とGATA3の相互作用によるTh1/Th2分化制御機構2008

    • Author(s)
      河府和義、大森秀孝、Wong Wen Fen、久保允人、佐竹正延
    • Organizer
      第18回京都T細胞会議
    • Place of Presentation
      京都
    • Year and Date
      2008-06-14
    • Related Report
      2008 Final Research Report
  • [Presentation] Regulation of non-canonical IL-17 expression by Memory phenotype (MP) CD4 T cells2008

    • Author(s)
      Tanaka, S., Kubo, M.
    • Organizer
      95^<th> Annual Meeting of the American Association of Immunologists (AAI)
    • Place of Presentation
      San Diego
    • Related Report
      2008 Final Research Report
  • [Presentation] IgE産生誘導にIL-4エンハンサーCNS-2は必須である2007

    • Author(s)
      田中 伸弥、久保允人
    • Organizer
      第17回京都T細胞会
    • Place of Presentation
      京都
    • Related Report
      2008 Final Research Report
  • [Presentation] I型ヘルパーT細胞におけるIL-13遺伝子の発現機構2007

    • Author(s)
      本村 泰隆、久保允人
    • Organizer
      第17回京都T細胞会議
    • Place of Presentation
      京都
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] A putative clock-controlled transcriptional factor, E4BP4/NFIL3 regulates selective IL-13 expression in chronic Th1 immune responses2007

    • Author(s)
      Motomura, Y., Azuma, T., Matsumoto, K., Inoue, H., Kubo, M.
    • Organizer
      The 37^<th> Annual Meeting of the Japanese Society for Immunology
    • Place of Presentation
      Tokyo
    • Related Report
      2008 Final Research Report
  • [Presentation] The regulation of IL-17A expression by memory-phenotype (MP) CD4 T cell2007

    • Author(s)
      Tanaka, S., Kubo, M.
    • Organizer
      The 37^<th> Annual Meeting of the Japanese Society for Immunology
    • Place of Presentation
      Tokyo
    • Related Report
      2008 Final Research Report
  • [Presentation] IgE産生誘導にIL-4エンハンサーCNS-2は必須である2007

    • Author(s)
      田中 伸弥
    • Organizer
      第17回京都T細胞会議
    • Place of Presentation
      京都
    • Related Report
      2007 Annual Research Report
  • [Book] 好塩基球によるIL-4遺伝子発現制御 アレルギー・免疫 vol.16, No. 3, p26-322009

    • Author(s)
      久保允人
    • Related Report
      2008 Final Research Report
  • [Book] 特集 T細胞研究新章:免疫疾患解明に向けた新たな展開、細胞工学 vol.27, No.2, 2-42008

    • Author(s)
      久保允人(監修)
    • Publisher
      秀潤社
    • Related Report
      2008 Final Research Report
  • [Book] Notchによるアレルギー・Th2分化制御、細胞工学、vol.27, No.2, p132-1362008

    • Author(s)
      田中伸弥・久保允人
    • Publisher
      秀潤社
    • Related Report
      2008 Final Research Report
  • [Book] PhosflowTM Technologyによるフローサイトメーターを用いたリン酸化STATの検出, BD Biosciences Phosflow Review, vol.1 p1-42008

    • Author(s)
      松野有希子、久保允人
    • Related Report
      2008 Final Research Report
  • [Book] 特集「ヘルパーT細胞の機構と分化制御」Th1/Th2 分子細胞治療 vol. 7,No.3, p107-1142008

    • Author(s)
      久保允人
    • Related Report
      2008 Final Research Report
  • [Book] アレルギーとエピジェネティクス 分子消化器病 vol. 5, No.4, p20-262008

    • Author(s)
      久保允人
    • Related Report
      2008 Final Research Report
  • [Book] メモリー型T細胞:アレルギー反応を制御する新たなT細胞サブセット、アレルギー・免疫、vol.14, No.2, 12-182007

    • Author(s)
      久保 允人
    • Related Report
      2008 Final Research Report
  • [Book] Th2細胞とマスト細胞におけるIL-4発現制御 臨床免疫 vol.47, No.1,26-322007

    • Author(s)
      田中伸弥、久保允人
    • Related Report
      2008 Final Research Report
  • [Book] 免疫応答と免疫病態の総合的分子理解に向けて、第II部 適応免疫からの展望、第10章Th1/Th2応答とクロマチン制御、77-862007

    • Author(s)
      久保允人
    • Publisher
      南山堂
    • Related Report
      2008 Final Research Report
  • [Patent(Industrial Property Rights)] IL-4初期発現系トランスジェニック非ヒト動物およびその利用2007

    • Inventor(s)
      田中伸弥,八木良二、久保允人
    • Industrial Property Rights Holder
      独立行政法人理化学研究所
    • Filing Date
      2007-02-22
    • Related Report
      2008 Final Research Report
  • [Patent(Industrial Property Rights)] アトピー性皮膚炎の発症予測診断方法、予防剤および治療剤

    • Inventor(s)
      吉田尚弘、安田琢和、若菜茂晴、久保允人
    • Industrial Property Rights Holder
      独立行政法人理化学研究所
    • Related Report
      2008 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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