Analysis of pathogenesis of immunological disorders by dysfunction of Runx transcriptional factor complexes

• Project/Area Number: 19390118
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: TANIUCHI Ichiro The Institute of Physical and Chemical Research, 免疫転写制御研究チーム, チームリーダー (20284573)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2008: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000); Fiscal Year 2007: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
• Keywords: 疾患モデル動物 / アレルギー / 炎症性腸疾患 / Runx転写因子 / マウスモデル / Tリンパ球 / インターロイキン4 / Th1 / Th2細胞 / IL4サイレンサー / インターロイキン-4 / IL-4サイレンサー

Research Abstract

Runx 転写因子機能不全に起因する免疫疾患の病態解明を主目的に研究を実施した。その結果、T細胞でのRunx機能不全により血清IgEの高値と肺への細胞浸潤といった喘息様疾患と炎症性腸炎が自然発症し、その発症機序にはIL-4サイレンサー機能制御不全によるIL-4過剰産生やSmad4を介したTGFβシグナル経路の異常が関与することを明らかにした。このような免疫疾患モデルマウスの樹立と免疫疾患の発症機序の解明は、新たな治療薬の開発に繋がるという研究成果と言える。

Research Products

• [Journal Article] RUNX proteins in transcription factor networks that regulate T-cell lineage choice (2009)
  • Author(s): Collins A, Littman D.R and Taniuchi I
  • Journal Title: Nat. Rev. Immunol 9 Pages: 106-15
  • Peer Reviewed
• [Journal Article] RUNX proteins in transcription factor networks that regulate T-cell lineage choice (2009)
  • Author(s): Ichiro Taniuchi
  • Journal Title: Nature Review Immunology 10 Pages: 106-115
  • Peer Reviewed
• [Journal Article] Cascading suppression of transcriptional silencers by ThPOK seals helper T cell fate (2008)
  • Author(s): Muroi S, Naoe Y, Miyamoto C, Akiyama K, Ikawa T, Masuda K, Kawamoto H and Taniuchi I
  • Journal Title: Nat. Immunol 9 Pages: 1113-21
  • Peer Reviewed
• [Journal Article] Notch 2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity (2008)
  • Author(s): Maekawa Y, Minato Y, Ishifune C, Kurihara T, Kitamura A, Kojima H, Yagita H, Satake-Yanagimoto M, Saito T, Taniuchi I, Chiba S, Sone S, and Yasutomo K
  • Journal Title: Nat. Immunol 9 Pages: 1140-47
  • Peer Reviewed
• [Journal Article] Repression of the Transcription Factor Th-POK by Runx Complexes in Cytotoxic T Cell Development (2008)
  • Author(s): Setoguchi R, Tachibana M, Naoe Y, Muroi S, Akiyama K, Tezuka C, Okuda T and Taniuchi I
  • Journal Title: Science 319 Pages: 816-819
  • Peer Reviewed
• [Journal Article] Cascading suppression of transcriptional silencers by ThPOK seals helper Tcell fate (2008)
  • Author(s): Ichiro Taniuchi
  • Journal Title: Nature Immunology 9 Pages: 1113-1121
  • Peer Reviewed
• [Journal Article] Repression of the transcription factor Th-POK by Runx complexes in cytoxic T cell development. (2008)
  • Author(s): Setoguchi R
  • Journal Title: Science. 319(5864): Pages: 822-5
  • Peer Reviewed
• [Journal Article] Repression of interleukin-4 in T helper type 1 cells by Runx/Cbfβ binding to the Il4 silencer (2007)
  • Author(s): Naoe Y, Setoguchi R, Akiyama K, Muroi S, Kuroda M, Hatam F, Littman D.R and Taniuchi I
  • Journal Title: J.Exp.Med 204 Pages: 1749-1755
  • Peer Reviewed
• [Journal Article] The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells (2007)
  • Author(s): Egawa T, Tillman R.E, Naoe Y, Taniuchi I and Littman D.R
  • Journal Title: J.Exp.Med 204 Pages: 1945-1957
  • Peer Reviewed
• [Journal Article] Runx1 protects hematopoietic stem/progenitor cells from oncogenic insult. (2007)
  • Author(s): Motoda L
  • Journal Title: Stem Cells 25(12) Pages: 2976-86
  • Peer Reviewed
• [Journal Article] The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells. (2007)
  • Author(s): Egawa T
  • Journal Title: J.ExpMed. 204 Pages: 1945-1957
  • Peer Reviewed
• [Journal Article] Repression of interleukin-4 in T helper type 1 cells by Runx/Cbfb binding to the 114 silencer. (2007)
  • Author(s): Naoe Y
  • Journal Title: J.ExpMed 204 Pages: 1749-1755
  • Peer Reviewed
• [Journal Article] Phosphorylation of Runx1 at Ser249,Ser266 and Ser276 is dispen sable for bone marrow hematopoiesis and thymocyte differentiation.
  • Author(s): Tachibana M
  • Journal Title: Biochem Biophys Res Commun. (in press)
  • Peer Reviewed
• [Presentation] Linege decision in Thymus (2009)
  • Author(s): Ichiro Taniuchi
  • Organizer: LIAI RCAI Joint Workshop
  • Place of Presentation: 理研構浜研究所
  • Year and Date: 2009-01-15
• [Presentation] Mechanism of Th-POK gene regulation during differentation of helper-lineage Tcells (2008)
  • Author(s): Ichiro Taniuchi
  • Organizer: Biochemistry and molecular biology
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] Roles of two enhancers at the ThPOK gene in regulating CD4+ helper Tcell development (2008)
  • Author(s): Ichiro Taniuchi
  • Organizer: 日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] Essential requirement of Cbfb isoform protain in regulating TG Fb-signaling by interacting with Smad protain (2008)
  • Author(s): Yoshinori Naoe
  • Organizer: 日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-01
• [Presentation] Transcriptional Regulation of Helper Lineage T Cell Development In Thymus (2008)
  • Author(s): Sawako Muroi
  • Organizer: 日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-01
• [Presentation] Role of Runx complexes during Tcell development (2008)
  • Author(s): Ichiro Taniuchi
  • Organizer: 15th International RUNX Workshop
  • Place of Presentation: Provincetown
  • Year and Date: 2008-09-15
• [Presentation] Mechanism of Th-POK gene regulation during differentiation of helper lineage Tcells (2008)
  • Author(s): Ichiro Taniuchi
  • Organizer: Wilsede Meeting
  • Place of Presentation: Hambrug
  • Year and Date: 2008-06-14
• [Presentation] Mechanism of Th-POK gene regulation during differentiation of helper lineage Tcells (2008)
  • Author(s): Ichiro Taniuchi
  • Organizer: CSH
  • Place of Presentation: ColiSpringHarbor Loboratry
  • Year and Date: 2008-04-24
• [Presentation] Essential requirement of Cbfb isoform protain in regulating TGFb-signaling by interacting with Smad protein (2008)
  • Author(s): 谷内 一郎
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] Role of Runx complexes during T cell development (2008)
  • Author(s): 谷内 一郎
  • Organizer: 15th International RUNX Workshop
  • Place of Presentation: Provincetown, USA
• [Presentation] Role of Runx proteins in early development of lymphoid tissue inducer cells (2007)
  • Author(s): 谷内 一郎
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] Transcriptional Factors Network in CD4/CD8 Lineage Choice (2007)
  • Author(s): 谷内 一郎
  • Organizer: RCAI-JSI International Symposium on Immunology 2007: Development and Maintenance of Immune System
  • Place of Presentation: 横浜
• [Presentation] Runx複合体のIL4 silencerへの結合を介したTh1細胞におけるIL4産生の抑制 (2007)
  • Author(s): 谷内 一郎
  • Organizer: 第17回Kyoto T Cell Conference (KTCC)
  • Place of Presentation: 京都
• [Remarks] ホームページ等
  • URL: http://web.rcai.riken.jp/en/labo/regu/
• [Patent(Industrial Property Rights)] T細胞特異的なサイレンサー活性を有するヌクレオチド及びその利用 (2007)
  • Inventor(s): 谷内一郎
  • Industrial Property Rights Holder: 独立行政法人理化学研究所
  • Filing Date: 2007-12-28
• [Patent(Industrial Property Rights)] 免疫疾患モデルマウスとしてのCbf2アイソフォーム欠損マウスの作製 (2006)
  • Inventor(s): 谷内一郎
  • Industrial Property Rights Holder: 独立行政法人理化学研究所
  • Filing Date: 2006-01-17
• [Patent(Industrial Property Rights)] 免疫疾患モデルマウスとしてのCbfβ2アイソフォーム欠損マウスの作製 (2006)
  • Inventor(s): 谷内 一郎
  • Industrial Property Rights Holder: 谷内 一郎
  • Industrial Property Number: 2006-008654
  • Filing Date: 2006-01-17