炎症性腸疾患の基盤的免疫学から臨床免疫内視鏡学の創成

2013 Fiscal Year Annual Research Report

• Project/Area Number: 23590949
• Research Institution: Keio University
• Principal Investigator: 岩男 泰 慶應義塾大学, 医学部, 教授 (40168547)
• Co-Investigator(Kenkyū-buntansha): 金井 隆典 慶應義塾大学, 医学部, 教授 (40245478)
• Keywords: 炎症性腸疾患 / alternative Th1 / 腸内細菌

Research Abstract

RORgt GFP/+マウスおよびRORgt KOマウスのnaive T細胞(CD4+CD45RBhigh)をRAG2欠損マウスに移入するadoptive transfer colitisモデルにおいてRORgt 陽性Th17細胞を介したTh1細胞分化経路が存在すること(alternative Th1)を証明し、このalternative Th1が強力な腸炎惹起性を有していること、制御性T細胞がこの経路を抑制することを明らかにした(Sujino et al. Gastroenterology. 2011 Sep;141(3):1014-23.)。さらに従来のclassical Th1細胞もRORgt 陽性細胞存在下で腸炎惹起性を有することも明らかにしつつある（論文準備中）。さらに腸内細菌叢のなかで酪酸産生菌Clostridium butyricumが予想されたTreg細胞でなく腸管マクロファージからのIL-10産生を促すことで強力な腸炎抑制効果を有することも明らかにした。ヒト炎症性腸疾患患者糞便を用いたフローラ解析の結果からもIBD患者でのClostridium butyricumの減少を確認しており臨床応用が期待できる。

Research Products

• [Journal Article] Macrophages and dendritic cells emerge in the liver during intestinal inflammation and predispose the liver to inflammation. (2014)
  • Author(s): Mikami Y, Mizuno S, Nakamoto N, Hayashi A, Sujino T, Sato T, Kamada N, Matsuoka K, Hisamatsu T, Ebinuma H, Hibi T, Yoshimura A, Kanai
  • Journal Title: PLoS One Volume: 9 Pages: e84619
  • DOI: 10.1371/journal.pone.0084619.
  • Peer Reviewed
• [Journal Article] Endoscopic and pathologic changes of the upper gastrointestinal tract in Crohn's disease. (2014)
  • Author(s): Sakuraba A, Iwao Y, Matsuoka K, Naganuma M, Ogata H, Kanai T, Hibi T. Endoscopic and pathologic changes of the upper gastroi ntestinal tract in Crohn's diseas
  • Journal Title: Biomed Res Int Volume: 2014 Pages: 610767
  • DOI: 10.1155/2014/610767. Epub 2014 Feb 3
  • Peer Reviewed
• [Journal Article] A single strain of Clostridium butyricum induces intestinal IL-10-producing macrophages to suppress acute experimental colitis in mice (2013)
  • Author(s): Hayashi A, Sato T, Kamada N, Mikami Y, Matsuoka K, Hisamatsu T, Hibi T, Roers A, Yagita H, Ohteki T, Yoshimura A, Kanai T
  • Journal Title: Cell Host Microbe Volume: 13(peer review) Pages: 711-22
  • DOI: 10.1016/j.chom.2013.05.013
• [Journal Article] Dendritic cells adminis tered intrarectally penetrate the intestinal barrier to break intestinal tolerance via Th2-medeiated colitis in mice (2013)
  • Author(s): Handa T, Kanai T, Sato T, Mikami Y, Sujino T, Hayashi A, Mizuno S, Matsumoto A, Hisamatsu T, Hibi T
  • Journal Title: Immuno l Let Volume: 150 Pages: 123-129
  • DOI: 10.1016/j.imlet.2013.01.010. Epub 2013 Jan 17.
  • Peer Reviewed
• [Journal Article] Long-term prognosis of patients with ulcerative colitis treated with cytapheresis therap (2013)
  • Author(s): Takayama T, Kanai T, Matsuoka K, Okamoto S, Sujino T, Mikami Y, Hisamatsu T, Yajima T, Iwao Y, Ogata H, Hibi T
  • Journal Title: J Crohns Colitis Volume: 7 Pages: e49-54
  • DOI: 10.1016/j.crohns.2012.05.005. Epub 2012 May 26.
  • Peer Reviewed
• [Journal Article] Mucosal healing with oral tacrolimus is associated with favorable medium- and long-term prognosis in steroid-refractory/dependent ulcerative colitis patients. (2013)
  • Author(s): Miyoshi J, Matsuoka K, Inoue N, Hisamatsu T, Ichikawa R, Yajima T, Okamoto S, Naganuma M, Sato T, Kanai T, Ogata H, Iwao Y, Hibi
  • Journal Title: J Crohns Colitis Volume: 7 Pages: e609-614
  • DOI: 10.1016/j.crohns.2013.04.018. Epub 2013 May 14.
  • Peer Reviewed