Research of Inflammatory Bowel Disease Based on Clinical Immunology and Endoscopy

• 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
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• 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. Endoscopic and pathologic changes of the upper gastroi ntestinal tract in Crohn's diseas
  • Journal Title: Biomed Res Int Volume: 2014 Pages: 610767-610767
  • DOI: 10.1155/2014/610767
  • Peer Reviewed
• [Journal Article] Macrophages and dendritic cells emerge in the liver during intestinal inflammation and predjspose 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 Issue: 1 Pages: 1-1
  • DOI: 10.1371/journal.pone.0084619
  • Peer Reviewed
• [Journal Article] A Single Strain of Clostridium butyricum Induces Intestinal I L-10-Producing Macrophages to Suppress Acute Exlperimental Colitis in Mice. (2013)
  • Author(s): Hayashi A, Sato T, Kamada N, Mikami Y, Matsuoka K, Hisamatsu T, Hlbi T, Roers A, Yagita H, Ohteki T, Yoshimura A, Kanai T.
  • Journal Title: Cell Host Microbe Volume: 13 Issue: 6 Pages: 711-22
  • DOI: 10.1016/j.chom.2013.05.013
  • 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 Issue: 12 Pages: e609-e614
  • DOI: 10.1016/j.crohns.2013.04.018
  • Peer Reviewed
• [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: Immunology Letters Volume: 150 Issue: 1-2 Pages: 123-9
  • DOI: 10.1016/j.imlet.2013.01.010
  • Peer Reviewed
• [Journal Article] Long-term prognosis of patients with ulcerative colitis treated with cytapheresis therapy. (2012)
  • 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: Journal of Crohns and Colitis Volume: 7 Issue: 2 Pages: e49-e54
  • DOI: 10.1016/j.crohns.2012.05.005
  • Peer Reviewed
• [Journal Article] Dysregulated balance of retinoid-related orphan receptor _Yt-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: Biochemical and Biophysical Research Communications Volume: 427 Issue: 4 Pages: 694-700
  • DOI: 10.1016/j.bbrc.2012.09.091
  • Peer Reviewed
• [Journal Article] Anti-high mobility group box 1 and box 2 non-histone chromosomal proteins (HMGB1/HMGB2) antibodies and anti-Saccharomyces cerevisiae antibodies(ASCA): accuracy in differentially diagnosing UC and CD and correlation with inflammatory bowel disease phenotype. (2012)
  • Author(s): Takaishi H, Kanai T, Nakazawa A, Sugata F, Nikai A, Yoshizawa S, Hamamoto Y, Funakoshi S, Yajima T, Iwao Y, Takemura M, Ozaki S, Hibi T.
  • Journal Title: J Gastroenterol. Volume: 47(9) Issue: 9 Pages: 969-977
  • DOI: 10.1007/s00535-012-0566-3
  • NAID: 10031122083
  • Peer Reviewed
• [Journal Article] Long-term prognosis of patients with ulcerative colitis treated with cytapheresis therapy. (2012)
  • 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: Journal of Crohn’s and Colitis. Volume: 7(2)
  • Peer Reviewed
• [Journal Article] Novel, objective, multivariate biomarkers composed of plasma amino acid profiles for the diagnosis and assessment of inflammatory bowel disease. (2012)
  • Author(s): Hisamatsu T, Okamoto S, Hashimoto M, Muramatsu T, Andou A, Uo M, Kitazume MT, Matsuoka K, Yajima T, Inoue N, Kanai T, Ogata H, Iwao Y, Yamakado M, Sakai R, Ono N, Ando T, Suzuki M ,Hibi T
  • Journal Title: PLoS ONE. Volume: 7(1)
  • Peer Reviewed
• [Journal Article] Novel technique of endoscopic submucosal dissection by using external forceps for early rectal cancer (with videos). (2012)
  • Author(s): Imaeda H, Hosoe N, Ida Y, Nakamizo H, Kashiwagi K, Kanai T, Iwao Y, Hibi T,Ogata H.
  • Journal Title: Gastrointest Endosc. Volume: 75 (6) Pages: 1253-1257
  • Peer Reviewed
• [Journal Article] The use of infliximab in the prevention of postsurgical recurrence in polysurgery Crohn's disease patients: a pilot open-labeled prospective study. (2012)
  • Author(s): Sakuraba A, Sato T, Matsukawa H, Okamoto S, Takaishi H, Ogata H, Iwao Y, Hibi T.
  • Journal Title: Int J Colorectal Dis. Volume: 27(7) Issue: 7 Pages: 947-952
  • DOI: 10.1007/s00384-011-1398-y
  • Peer Reviewed
• [Journal Article] 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, et al
  • Journal Title: Gastroenterology Volume: 141 Issue: 3 Pages: 1014-1023
  • DOI: 10.1053/j.gastro.2011.05.052
  • Peer Reviewed
• [Journal Article] Ectopic expression of blood type antigens in inflamed mucosa with higher incidence of FUT2 secretor status in colonic Crohn's disease (2011)
  • Author(s): Miyoshi J, Yajima T, Okamoto S, Matsuoka K, Inoue N, Hisamatsu T, Shimamura K, Nakazawa A, Kanai T, Ogata H, Iwao Y, Mukai M, Hibi
  • Journal Title: J Gastroenterol Volume: 46( 9) Pages: 1056-1063
  • NAID: 10029706720
  • Peer Reviewed
• [Journal Article] Target biopsy or step biopsy? Optimal surveillance for ulcerative colitis: a Japanese nationwide randomized controlled trial. (2011)
  • Author(s): Watanabe T, Ajioka Y, Igarashi M, Iwao Y, Ohtsuka K, Kudo SE, Kobayashi K, Sada M, Matsumoto T, Hirata I, Murakami K, Nagahori M, Watanabe K, Hida N, Ueno F, Tanaka S, Watanabe M, Hibi T
  • Journal Title: J Gastroenterol Volume: 46 Suppl 1 Pages: 11-16
  • NAID: 10029029994
  • Peer Reviewed
• [Journal Article] Oncogenic Smad3 signaling induced by chronic inflammation is an early event in ulcerative colitis-associated carcinogenesis. (2011)
  • Author(s): Kawamata S, Matsuzaki K, Murata M, Seki T, Matuoka M, Iwao Y, Hibi T, Okazaki K.
  • Journal Title: Inflamm Bowel Dis Volume: 17 Pages: 683-695
  • Peer Reviewed
• [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
• [Presentation] Anti-viral therapy is not necessarily indicated in ulcerative colitis patients with cytomegalovirus infection detected by immunohistochemistry. (2012)
  • Author(s): Maruyama Y, Matsuoka K, Iwao Y, Yajima T, Inoue N, Hisamatsu T, Sujino T, Takabayashi K, Yoneno K, Mikami Y, Miyoshi J, Mizuno S, Kimura K, Kanai T, Ogata H, Mukai M, Hibi T.
  • Organizer: Digestive Disease Week 2012
  • Place of Presentation: San Diego, USA
• [Presentation] Complete mucosal healing is associated with long-term remission in ulcerative colitis. (2012)
  • Author(s): Inoue N, Takabayashi K, Matsuoka K, Hisamatsu T, Kanai T, Ogata H, Iwao Y, Hibi T.
  • Organizer: Digestive Disease Week 2012
  • Place of Presentation: San Diego, USA
• [Presentation] Early normalization of C-reactive protein (CRP)by infliximab is a predictive factor of sustained long-term clinical efficacy in crohn’s disease. (2012)
  • Author(s): Kimura K, Matsuoka K, Kanai T, Okamoto S, Hisamatsu T, Inoue N, Yajima T, Ogata H, Iwao Y, Hibi T.
  • Organizer: The 14th Meeting of International Conference on Ulcer Research
  • Place of Presentation: Tokyo
• [Presentation] Novel technique of endoscopic submucosal dissection using external forceps for early rectal cancer. (2012)
  • Author(s): Imaeda H, Hosoe N, Ida Y, Nakamizo H, Kashiwagi H, Kanai T, Iwao Y, Hibi T, Ogata H.
  • Organizer: The 14th Meeting of International Conference on Ulcer Research.
  • Place of Presentation: Tokyo
• [Presentation] A case report of infliximab use in pregnant UC patient exacerbating with a complication of CMV colitis. (2012)
  • Author(s): Tsukagoshi U, Saigusa K, Yajima T, Hisamatsu T , Matuoka K, Naganuma M, Inoue N, Kanai T, Ogata H, Iwao Y, Hibi T.
  • Organizer: Asian IBD Symposium Seoul 2012
  • Place of Presentation: Seoul, Korea