Regulatory signaling in intestinal dendritic cells preventing inflammatory bowel diseases

• Project/Area Number: 19390137
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: HONDA Kenya Osaka University, 医学系・研究科, 准教授 (60334231)
• Co-Investigator(Renkei-kenkyūsha): TAKEDA Kiyoshi 大阪大学, 医学系研究科, 教授 (20309446) ; TAYA Chouji 東京都医学研究機構, 研究員 (90175456) ; OHBA Yusuke 北海道大学, 医学系研究科, 准教授 (30333503)
• 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: サイトカイン / 粘膜免疫 / 樹状細胞 / イメージング / インターロイキン / IL-10 / STAT / IRF

Research Abstract

腸管樹状細胞を機能的に細分化し、シグナル伝達機構を明らかにし、炎症性腸疾患との関わりを検討することを目的として研究を推進した。新たにCD70が活性化型と抑制型樹状細胞を区別するバイオマーカーとして利用できることが明らかにした。CD70は消化管粘膜固有層特異的に存在する樹状細胞集団の一部において高発現しており、他の臓器にはそのような細胞を認めなかった。更にCD70陽性粘膜固有層樹状細胞は、細胞外ATPの受容体であるP2XやP2Y受容体を高発現しており、ATP刺激によって、共培養したナイーブCD4T細胞をIL17を高産生するTH17細胞へと分化させることも見出した。即ちCD70陽性粘膜固有層樹状細胞は"活性化型樹状細胞"であると考えられた。

Research Products

• [Journal Article] Regulatory mechanisms of immune responses to intestinal bacteria (2009)
  • Author(s): Honda K, Takeda K.
  • Journal Title: Mucosal Immunol 2 Pages: 187-96
  • Peer Reviewed
• [Journal Article] Hematopoietic cell derived interferon controls viral replication and virus induced disease (2009)
  • Author(s): Lang PA, Cervantes-Barragan L, Verschoor A, Navarini AA, Recher M, Pellegrini M, Flatz L, Bergthaler A, Honda K, Ludewig B, Ohashi PS, Lang KS
  • Journal Title: Blood 113 Pages: 1045-52
  • Peer Reviewed
• [Journal Article] Triggering TLR7 in mice induces immune activation and lymphoid system disruption, resembling HIV-mediated pathology (2009)
  • Author(s): Baenziger S, Heikenwalder M, Johansen P, Schlaepfer E, Hofer U, Miller RC, Diemand S, Honda K, Kundig TM, Aguzzi A, Speck RF
  • Journal Title: Blood 113 Pages: 377-88
  • Peer Reviewed
• [Journal Article] ATP drives lamina propria T(H)17 cell differentiation (2008)
  • Author(s): Atarashi K, Nishimura J, Shima T, Umesaki Y, Yamamoto M, Onoue M, Yagita H, Ishii N, Evans R, Honda K, Takeda K.
  • Journal Title: Nature 455 Pages: 808-12
  • Peer Reviewed
• [Journal Article] A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity (2008)
  • Author(s): Negishi H, Osawa T, Ogami K, Ouyang X, Sakaguchi S, Koshiba R, Yanai H, Seko Y, Shitara H, Bishop K, Yonekawa H, Tamura T, Kaisho T, Taya C, Taniguchi T, Honda K
  • Journal Title: PNAS 105 Pages: 20446-51
  • Peer Reviewed
• [Journal Article] Lipocalin 2-dependent inhibition of mycobacterial growth in alveolar epithelium (2008)
  • Author(s): Saiga H, Nishimura J, Kuwata H, Okuyama M, Matsumoto S, Sato S, Matsumoto M, Akira S, Yoshikai Y, Honda K, Yamamoto M, Takeda K
  • Journal Title: J Immunol 181 Pages: 8521-7
  • Peer Reviewed
• [Journal Article] Inefficient phagosome maturation in infant macrophages (2008)
  • Author(s): Saito F, Kuwata H, Oiki E, Koike M, Uchiyama Y, Honda K, Takeda K.
  • Journal Title: BBRC 375 Pages: 113-8
  • Peer Reviewed
• [Journal Article] Class-specific Regulation of Pro-inflammatory Genes by MyD88 Pathways and IkBz (2008)
  • Author(s): Kayama H, Ramirez-Carrozzi VR, Yamamoto M, Mizutani T, Kuwata H, Iba H, Matsumoto M, Honda K, Smale ST, Takeda K
  • Journal Title: J Biol Chem 283 Pages: 12468-77
  • Peer Reviewed
• [Journal Article] Homeostatic erythropoiesis by the transcription factor IRF2 through attenuation of type I interferon signaling (2008)
  • Author(s): Mizutani, T., K. Tsuji, Y. Ebihara, S. Taki, Y. Ohba, T. Taniguchi, K. Honda
  • Journal Title: Exp Hematol 36 Pages: 255-64
  • Peer Reviewed
• [Journal Article] The contribution of transcription factor IRF1 to the interferon-gamma-interleukin 12 signaling axis and T(H)1 versus T(H)-17 differentiation of CD4(+) T cells (2008)
  • Author(s): Kano SI., Sato K., Morishita Y., Vollstedt S., Kim S., Bishop K., Honda K., Kubo M., Taniguchi T.
  • Journal Title: Nature Immunology 9 Pages: 34-41
  • Peer Reviewed
• [Journal Article] ATP drives lamina propr ia T(H)17 cell differentiation. (2008)
  • Author(s): Atarashi K, (他8名), Honda K, Takeda K.
  • Journal Title: Nature 455 Pages: 808-812
  • Peer Reviewed
• [Journal Article] A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity. (2008)
  • Author(s): Negi shi H, (他14名), HondaK.
  • Journal Title: Proc Natl Acad Sci U S A. 105 Pages: 20446-51
  • Peer Reviewed
• [Journal Article] Homeostatic erythropoiesis by the transcription factor IRF2 through attenuation of type I interferon signaling. (2008)
  • Author(s): Mizutani, T., et. al.
  • Journal Title: Experimental Hematology 36 Pages: 255-264
  • Peer Reviewed
• [Journal Article] DAI(DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response (2007)
  • Author(s): Takaoka A, Wang Z, Choi MK, Yanai H, Negishi H, Ban T, Lu Y, Miyagishi M, Kodama T, Honda K, Ohba Y, Taniguchi T
  • Journal Title: Nature 448 Pages: 501-5
  • Peer Reviewed
• [Journal Article] The contribution of transcription factor IRF1 to the interferon-gamma-interleukin 12 signaling axis and T(H)1 versus T(H)-17 differentiation of CD4(+)T cells. (2007)
  • Author(s): Kano, SI., et. al.
  • Journal Title: Nature Immunology 9 Pages: 34-41
  • Peer Reviewed
• [Journal Article] DAI(DLM-1/ZBP1)is a cytosolic DNA sensor and an activator of innate immune response. (2007)
  • Author(s): Takaoka, A., et. al.
  • Journal Title: Nature 448 Pages: 501-505
  • Peer Reviewed
• [Presentation] 腸内フローラによるTH17 細胞誘導 (2009)
  • Author(s): 本田賢也、新幸二、竹田潔
  • Organizer: 第82回日本細菌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-03-12
• [Presentation] Extracellular ATP drives lamina propria TH17 cell differentiation (2008)
  • Author(s): Kenya Honda, Koji Atarashi, Junichi Nishimura, Kiyoshi Takeda
  • Organizer: BMB2008
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] Extracellular ATP activates intestinal lamina propria dendritic cells to induce TH17 cells (2008)
  • Author(s): Kenya Honda
  • Organizer: 第10回国際樹状細胞シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2008-10-03
• [Presentation] Extracellular ATP activates intestinal lamina propr iadendri tic cells to induce TH17 cells (2008)
  • Author(s): Kenya Honda
  • Organizer: 第10回国際樹状細胞シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2008-10-03
• [Presentation] Extracellular ATP from commensal bacteria drives lamina propria TH17 cell differentiation (2008)
  • Author(s): Kenya Honda, Koji Atarashi, Junichi Nishimura, and Kiyoshi Takeda
  • Organizer: JSI-RCAI Workshop 2008 粘膜免疫機構の制御と破綻
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-14
• [Presentation] Commensal bacteria-derived ATP drives lamina propria TH17 cells (2008)
  • Author(s): Kenya Honda
  • Organizer: Colloquium for the study of gastrointestinal defense system
  • Place of Presentation: Kitano Hospital, Osaka
  • Year and Date: 2008-01-12
• [Presentation] Extracellular ATP from commensal bacteria drives lamina propria TH17 cell differentiation (2008)
  • Author(s): Kenya Honda, Koji Atarashi, Junichi Nishimura, and Kiyoshi Takeda
  • Organizer: Cold Spring Harbor Laboratory Meeting
  • Place of Presentation: New York
• [Book] 「免疫系細胞における遺伝子発現の時空間制御」[免疫応答と免疫病態の統合的分子理解](谷口維紹、山本一彦編) (2007)
  • Author(s): 本田賢也
  • Publisher: 南山堂
• [Book] 免疫応答と免疫病態の統合的分子理解…免疫系細胞における遺伝子発現の時空間制御 (2007)
  • Author(s): 本田賢也, ら
  • Total Pages: 269
  • Publisher: 南山堂
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/ongene/project1.html
• [Remarks] 発表論文は、日経新聞2008.8.28、読売新聞2008.8.22等に紹介された
  • URL: http://www.med.osaka-u.ac.jp/pub/ongene/projectl.html
• [Remarks]
  • URL: http://www.ifrec.osaka-u.ac.jp/jpn/research/2008/08/nature-takeda080829.php
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/ongene/index.html