Epigenetic dysregulation of immune responses in inflammatory bowel disease

• Project/Area Number: 25460965
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: Kawamura Yuki I. 国立研究開発法人国立国際医療研究センター, 研究所・肝炎・免疫研究センター・消化器疾患研究部, 消化器病態生理研究室長 (10392391)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 炎症性腸疾患 / エピジェネティクス / エピゲノム

Outline of Final Research Achievements

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, are characterized by relapsing/remitting nature of the inflammatory process. The aim of this study was to find out key epigenetic alterations in IBD. We established the methods for epigenomic analysis for small number of isolated cells from patients with IBD. Immune cells isolated from lamina propria mononuclear cells were subjected to a chromatin immunoprecipitation (ChIP) with anti-H3K4me3, anti-H3K9me3 and anti-H3K27me3 antibodies, and ChIPed DNA was analyzed by the next generation sequencer system. Bioinformatic analysis identified the IBD-specific epigenetic dysregulation in immune cells.

Research Products

• [Journal Article] Interferon-gamma Constrains Cytokine Production of Group 2 Innate Lymphoid Cells (2016)
  • Author(s): Kudo, F. Ikutani, M. Seki, Y. Otsubo, T. Kawamura, Y. I. Dohi, T. Oshima, K. Hattori, M. Nakae, S. Takatsu, K. Takaki, S.
  • Journal Title: Immunology Volume: 147 Issue: 1 Pages: 21-29
  • DOI: 10.1111/imm.12537
  • Peer Reviewed
• [Journal Article] Retrotransposition of long interspersed nucleotide element-1 is associated with colitis but not tumors in a murine colitic cancer model. (2015)
  • Author(s): Otsubo T, Okamura T, Hagiwara T, Ishizaka Y, Dohi T, Kawamura YI.
  • Journal Title: PLoS One Volume: 10 (2) Issue: 2 Pages: e0116072-e0116072
  • DOI: 10.1371/journal.pone.0116072
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The epigenetic regulator Uhrf1 facilitates proliferation and maturation of colonic regulatory T cells (2014)
  • Author(s): Yuuki Obata*, Yukihiro Furusawa*, Takaho A. Endo, Jafar Sharif, Daisuke Takahashi, Koji Atarashi, Manabu Nakayama, Satoshi Onawa, Yumiko Fujimura, Masumi Takahashi, Tomokatsu Ikawa, Takeshi Otsubo, Yuki I. Kawamura, Taeko Dohi, Shoji Tajima, Osamu Ohara, Kenya Honda, Shohei Hori, Hiroshi Ohno, Haruhiko Koseki and Koji Hase. 【* : 筆頭筆者】
  • Journal Title: Nature Immunology Volume: 15 Issue: 6 Pages: 571-579
  • DOI: 10.1038/ni.2886
  • Peer Reviewed / Open Access
• [Presentation] Sialic-acid-binding Ig-like lectines, potential peripheral markers for mucosal damage of inflammatory bowel disease. (2015)
  • Author(s): Kawamura YI, Maeyashiki C, Hagiwara T, Otsubo T, Akiyama J, Dohi T.
  • Organizer: United European Gastroenterology Week Annual Meeting
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2015-10-22
• [Presentation] 消化器疾患で見られる糖鎖異常とエピジェネティックな遺伝子サイレンシング (2015)
  • Author(s): 河村由紀
  • Organizer: 日本糖質学会年会
  • Place of Presentation: 東京
  • Year and Date: 2015-07-31
  • Invited
• [Presentation] 潰瘍性大腸炎における粘膜固有層免疫細胞のエピゲノム異常 (2015)
  • Author(s): 河村由紀、大坪武史、大島健志朗、豊田哲郎、萩原輝記、河村裕、小西文雄、矢野秀朗、斉藤幸夫、服部正平、土肥多恵子
  • Organizer: 日本消化器免疫学会総会
  • Place of Presentation: 東京
  • Year and Date: 2015-07-31