Research of Inflammatory Bowel Disease Based on Clinical Immunology and Endoscopy

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590949
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Keio University
• Principal Investigator: IWAO Yasushi 慶應義塾大学, 医学部, 教授 (40168547)
• Co-Investigator(Kenkyū-buntansha): KANAI Takanori 慶應義塾大学, 医学部, 教授 (40245478)
• Project Period (FY): 2011 – 2013
• Keywords: 炎症性腸疾患 / alternative Th1 / 腸内細菌

Research Abstract

In CD4+CD45RBhigh adoptive transfer colitis model, we demonstrated that RORgt+ Th17 and Th17/Th1 cells become colitogenic alternative Th1 cells in vivo. Treg cells suppressed this pathway and development of intestinal inflammation. In addition, we found that Clostridium butyricum, which produces butyrate, suppress intestinal inflammation in mice colitis models. Interestingly, C. butyricum promoted IL-10 production by intestinal macrophage, but not Treg cells. Fecal 16S rRNA analysis, C. butyricum was decreased in the patients with IBD. Our findings provide the new insight into the mechanism of colitogenic T cell development in vivo and suggests the potential of Clostridium butyricum as a novel probiotics.

Research Products

• [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
  • Journal Title: Biomed Res Int Volume: 89(peer review) Pages: e610767
  • DOI: 10.1155/2014/610767
• [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 T
  • Journal Title: PLoS One Volume: 9(peer review) Pages: e84619
  • DOI: 10.1371/journal.pone.0084619
• [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] 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 T
  • Journal Title: J Crohns Colitis Volume: 7(peer review) Pages: e609-14
  • DOI: 10.1016/j.crohns.2013.04.018
• [Journal Article] Dendritic cells administered 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: Immunol Lett Volume: 150(peer review) Pages: 23-9
  • DOI: 10.1016/j.imlet.2013.01.010
• [Journal Article] Long-term prognosis of patients with ulcerative colitis treated with cytapheresis therapy (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(peer review) Pages: e49-54
  • DOI: 10.1016/j.crohns.2012.05.005
• [Journal Article] Dysregulated balance of retinoid-related orphan receptorγt-dependent innate lymphoid cells is involved in the pathogenesis of chronic DSS-induced colitis (2012)
  • Author(s): Kimura K, Kanai T, Hayashi A, Mikami Y, Sujino T, Mizuno S, Handa T, Matsuoka K, Hisamatsu T, Sato T, Hibi T
  • Journal Title: Biochem Biophys Res Commun Volume: 427(peer review) Pages: 694-700
  • DOI: 10.1016/j.bbrc.2012.09.091
• [Journal Article] Littman DR< Hibi T. Regulatory T cells suppress development of colitis, blocking differentiation of T-helper 17 into alternative T-helper 1 cells (2011)
  • Author(s): Sujino T, Kanai T, Ono Y, Mikami Y, Hayashi A, Doi T, Matsuoka K, Hisamatsu T, Takaishi H, Ogata H, Yoshimura A
  • Journal Title: Gastroenterology Volume: 141(peer review) Pages: 1014-23
  • DOI: 10.1053/j.gastro.2011.05.052
• [Presentation] A Single Strain of Clostridium Butyricum Suppresses Intestinal Inflammation by Converting Activated Lamina Propria Cd11b+CD11cInt Macrophages to IL-10-Producing Regulatory Macrophages (2012)
  • Author(s): Hayashi A, et al
  • Organizer: American Gastroenterology Association
  • Place of Presentation: San Diego, USA
  • Year and Date: 2012-05-21
• [Presentation] Intestinal Microbiota is Essential for Both the Initiation and the Maintenance of Colitis,and Dysbiosis of IBD Patients (2012)
  • Author(s): Sujino T, et al
  • Organizer: The 98th General Meeting of the Japanese Society of Gastroenterology
  • Place of Presentation: Tokyo
  • Year and Date: 2012-04-20