Characterization of intestinal microbiota for the treatment of inflammatory bowel disease

• Project/Area Number: 23790524
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: The Institute of Physical and Chemical Research (2012); The University of Tokyo (2011)
• Principal Investigator: ATARASHI Koji 独立行政法人理化学研究所, 免疫細胞システム研究グループ, 客員研究員 (60546787)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 制御性T 細胞 / 腸内細菌 / 炎症性腸疾患 / Treg / Clostridium / IL-10 / 腸管免疫 / 制御性T細胞

Research Abstract

Many studies suggest that altered intestinal microbiota may play a major role in the onset and exacerbation of several inflammatory diseases, including inflammatory bowel diseases (IBDs). We previously reported that murine commensal bacteria Clostridium spp. have the capacity to induce intestinal regulatory T (Treg) cells. This study was focused on the human intestinal bacteria which can induce Treg cells in the intestine. I successfully isolated the bacteria with the ability to induce Treg cells from human stool, and administration of these bacteria attenuated disease in models of colitis and allergic diarrhea.

Research Products

• [Journal Article] Transcriptional reprogramming of mature CD4+ helper T cells generates distinct MHC class II?restricted cytotoxic T lymphocytes. (2013)
  • Author(s): Mucida D, Husain MM, Muroi S, van Wijk F, Shinnakasu R, Naoe Y, Reis BS, Huang Y, Lambolez F, Docherty M, Attinger A, Shui JW, Kim G, Lena CJ, Sakaguchi S, Miyamoto C, Wang P, Atarashi K, Park Y, Nakayama T, Honda K, Ellmeier W, Kronenberg M, Taniuchi I, Cheroutre H.
  • Journal Title: Nat Immunol. Volume: 14 Pages: 281-289
  • Peer Reviewed
• [Journal Article] Ecto-nucleoside triphosphate diphosphohydrolase 7 controls Th17 cell responses through regulation of luminal ATP in the small intestine (2013)
  • Author(s): Kusu T, Kayama H, Kinoshita M, Jeon SG, Ueda Y, Goto Y, Okumura R, Saiga H, Kurakawa T, Ikeda K, Maeda Y, Nishimura J, Arima Y, Atarashi K, Honda K, Murakami M, Kunisawa J, Kiyono H, Okumura M, Yamamoto M, Takeda K.
  • Journal Title: J Immunol. Volume: 190 Pages: 774-783
  • Peer Reviewed
• [Journal Article] Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses. (2012)
  • Author(s): Negishi H, Yanai H, Nakajima A, Koshiba R, Atarashi K, Matsuda A, Matsuki K, Miki S, Doi T, Aderem A, Nishio J, Smale ST, Honda K, and Taniguchi T.
  • Journal Title: Nat Immunol. Volume: 13 Pages: 659-666
  • Peer Reviewed
• [Journal Article] Microbiota in autoimmunity and tolerance. (2011)
  • Author(s): Atarashi K, Honda K.
  • Journal Title: Curr Opin Immunol. Volume: 23 Pages: 761-768
  • Peer Reviewed
• [Journal Article] Microbiotal influence on T cell subset development (2011)
  • Author(s): Atarashi K, Umesaki Y, Honda K.
  • Journal Title: Semin Immunol Volume: 23 Pages: 146-153
  • Peer Reviewed
• [Journal Article] Induction of colonic regulatory T cells by indigenous Clostridium species (2011)
  • Author(s): K. Atarashi, T. Tanoue, T. Shima, A. Imaoka, T. Kuwahara, Y. Momose, G. Cheng, S. Yamasaki, T. Saito, Y. Ohba, T. Taniguchi, K. Takeda, S. Hori, I.I. Ivanov, Y. Umesaki, K. Itoh and K. Honda
  • Journal Title: Science Volume: 331 Issue: 6015 Pages: 337-341
  • DOI: 10.1126/science.1198469
  • Peer Reviewed
• [Journal Article] Microbiota in autoimmunity and tolerance. (2011)
  • Author(s): Atarashi, K. ;Honda, K.
  • Journal Title: Curr Opin Immunol Volume: 23 Issue: 6 Pages: 761-768
  • DOI: 10.1016/j.coi.2011.11.002
  • Peer Reviewed
• [Journal Article] Microbiotal influence on T cell subset development (2011)
  • Author(s): Atarashi, K. ;Umesaki, Y. ;Honda, K.
  • Journal Title: Seminars in Immunology Volume: 23 Issue: 2 Pages: 146-153
  • DOI: 10.1016/j.smim.2011.01.010
  • Peer Reviewed
• [Presentation] Human clostridium species promote intestinal accumulation of Treg cells (2013)
  • Author(s): Atarashi K
  • Organizer: Keystone Symposia "The Gut Microbiome: The Effector/Regulatory Immune Network"
  • Place of Presentation: Taos, New Mexico
  • Year and Date: 2013-02-11
• [Presentation] 腸内細菌によるT 細胞応答の誘導 (2013)
  • Author(s): 新幸二
  • Organizer: 第46回日本無菌生物ノートバイオロジー学会総会
  • Place of Presentation: 神奈川県伊勢原市
  • Year and Date: 2013-01-25
• [Presentation] Human clostridium species promote intestinal accumulation of Treg cells (2013)
  • Author(s): Koji Atarashi
  • Organizer: Keystone Symposia “The Gut Microbiome: The Effector/Regulatory Immune Network”
  • Place of Presentation: Sagebrush Inn and Conference Center (Taos, New Mexico)
• [Presentation] 腸内細菌によるT細胞応答の誘導 (2013)
  • Author(s): 新幸二
  • Organizer: 第46回日本無菌生物ノートバイオロジー学会総会
  • Place of Presentation: FORUM246 (神奈川県伊勢原市)
  • Invited
• [Presentation] Induction of intestinal Regulatory T cells by Human Clostridium species (2012)
  • Author(s): Atarashi K
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2012-12-07
• [Presentation] Induction of intestinal Regulatory T cells by Human Clostridium species (2012)
  • Author(s): Koji Atarashi
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 国際会議場 (兵庫県神戸市)
• [Presentation] 腸管でのT 細胞誘導における腸内細菌の役割 (2011)
  • Author(s): 新幸二
  • Organizer: 食品免疫学会第6回宿泊セミナー
  • Place of Presentation: 東京都台東区
  • Year and Date: 2011-11-26
• [Book] Microbial Recognition and Pathogen-Associated Molecular Pattern Receptors in Inflammatory Bowel Disease Crohn's Disease and Ulcerative Colitis. (2012)
  • Author(s): Honda K, Atarashi K, Nishio J.
• [Book] 実験医学 (2011)
  • Author(s): 新幸二 ;本田賢也
  • Publisher: 腸内細菌によるT細胞誘導
• [Book] 炎症と免疫 (2011)
  • Author(s): 新幸二 ;本田賢也
  • Publisher: 消化管IL-17産生細胞と制御性T細胞の分化と機能
• [Patent(Industrial Property Rights)] Composition for inducing proliferation or accumulation of regulatory t cells (2011)
  • Inventor(s): HONDA Kenya、ATARASHI Koji、ITOH Kikuji, TANOUE Takeshi
  • Industrial Property Rights Holder: The University Of Tokyo
  • Filing Date: 2011-06-03
  • Overseas
• [Patent(Industrial Property Rights)] Composition, useful for e.g. treating chronic inflammatory bowel disease, and rheumatoid arthritis, comprises bacteria of Clostridium or active substance derived from bacteria (2011)
  • Inventor(s): 本田賢也、新幸二、伊藤喜久治、田之上大
  • Industrial Property Rights Holder: 本田賢也、新幸二、伊藤喜久治、田之上大
  • Filing Date: 2011
  • Acquisition Date: 2011
  • Overseas