Competition between colitogenic Th1 and Th17 cells as a new concept of IBD pathogenesis and new therapeutic target.

2011 Fiscal Year Final Research Report

• Project/Area Number: 22790667
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Keio University
• Principal Investigator: MIKAMI Yohei 慶應義塾大学, 医学部, 研究員(非常勤) (80528662)
• Project Period (FY): 2010 – 2011
• Keywords: 炎症性腸疾患 / インターロイキン17 / インターフェロンガンマ / クローナルコンペティション

Research Abstract

In this study, we showed that the interaction between Th17 cells and Th1 cells contribute to altering disease phenotypes. We have also demonstrated that Th17 and Th17/Th1 cells become colitogenic alternative Th1 cells via Th17, Th17/Th1, and Th1-like cells, independently of classical Th1 cells. We have also established that regulatory T cells suppress this pathway, resulting in accumulation of Th17 and Th17/Th1 cells. This alternative pathway, generating colitogenic Th1 cells, could be a new therapeutic target of Inflammatory bowel diseases(IBD).

Research Products

• [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, Hayashi A, Doi T, Matsuoka K, Hisamatsu T, Takaishi H, Ogata H, Yoshimura A, Littman DR, Hibi T
  • Journal Title: Gastroenterology Volume: 141(3) Pages: 1014-23
  • Peer Reviewed
• [Journal Article] Competition between colitogenic Th1 and Th17 cells contributes to the amelioration of colitis (2010)
  • Author(s): Mikami Y, Kanai T, Sujino T, Ono Y, Hayashi A, Okazawa A, Kamada N, Matsuoka K, Hisamatsu T, Okamoto S, Takaishi H, Inoue N, Ogata H, Hibi T
  • Journal Title: Eur J Immunol Volume: 40(9) Pages: 2409-22
  • Peer Reviewed
• [Journal Article] MyD88-dependent pathway accelerates the liver damage of Concanavalin A-induced hepatitis (2010)
  • Author(s): Ojiro K, Ebinuma H, Nakamoto N, Wakabayashi K, Mikami Y, Ono Y, Po-Sung C, Usui S, Umeda R, Takaishi H, Yamagishi Y, Saito H, Kanai T, Hibi T
  • Journal Title: Biochem Biophys Res Commun Volume: 399(4) Pages: 744-9
  • Peer Reviewed
• [Presentation] 腸炎モデルマウスにおける肝免疫攪乱 (2012)
  • Author(s): Yohei Mikami
  • Organizer: 消化管学会総会
  • Place of Presentation: 仙台国際センター, Sendai
  • Year and Date: 2012-02-10
• [Presentation] Liver tolerance is maintained by tolerogenic immature CCR9+pDCs and their breakdown is caused by activated macrophages in IBD model mice (2011)
  • Author(s): Yohei Mikami
  • Organizer: 15th International Conference of Mucosal Immunology
  • Place of Presentation: Paris, France
  • Year and Date: 2011-07-07
• [Presentation] 炎症性腸疾患においてCD4+CD25+制御性T細胞におけるTh1/Th17細胞バランス是正機構 (2011)
  • Author(s): Yohei Mikami
  • Organizer: The 35th Annual Meeting of the Japanese Society of Lymphology
  • Place of Presentation: 東京ステーションコンファレンス, Tokyo
  • Year and Date: 2011-06-03
• [Presentation] 炎症性腸疾患マウスにおける肝臓内抗原提示細胞の撹乱 (2011)
  • Author(s): Yohei Mikami
  • Organizer: 消化器病学会総会
  • Place of Presentation: Keio Plaza Hotel, Tokyo
  • Year and Date: 2011-05-15
• [Presentation] The breakdown of liver tolerance in colitic conditions induced by the disappearance of immature CCR9+pDCs and the emergence of activated macrophages in liver (2011)
  • Author(s): Yohei Mikami
  • Organizer: Digestive Disease Week 2011
  • Place of Presentation: Chicago
  • Year and Date: 2011-05-08
• [Presentation] T-bet分子を発現する腸炎惹起性Th1 CD4 T細胞とTh17から発生するTh1様CD4 T細胞 (2011)
  • Author(s): Yohei Mikami
  • Organizer: 消化管学会総会(workshop)
  • Place of Presentation: Kyoto
  • Year and Date: 2011-02-10
• [Presentation] Competition between colitogenic T helper 1 and 17 CD4+T cells contributes to the amelioration of colitis (2010)
  • Author(s): Yohei Mikami
  • Organizer: The 4th Japan and US Collaboration Conference in Gastroenterology, Digestive Diseases and Sciences
  • Place of Presentation: Tokyo
  • Year and Date: 2010-11-18
• [Presentation] Competition between colitogenic T helper 1 and 17 CD4+T cells contributes to the amelioration of colitis (2010)
  • Author(s): Yohei Mikami
  • Organizer: US-Japan GI Executive Meeting 2010
  • Place of Presentation: Tokyo
  • Year and Date: 2010-06-18
• [Presentation] Competition between colitogenic T helper 1-and 17-CD4+T cells contributes to the amelioration of colitis (2010)
  • Author(s): Yohei Mikami
  • Organizer: Digestive Disease Week 2010
  • Place of Presentation: New Orleans
  • Year and Date: 2010-05-05
• [Remarks]
  • URL: http://www.keio-med.jp/gastro/