Elucidation of intestinal mucosal immune system through the intracellular processing mechanisms of bacteria and its application for novel therapy of inflammatory bowel disease

2010 Fiscal Year Final Research Report

• Project/Area Number: 20200080
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology; Immunology
• Research Institution: Keio University
• Principal Investigator: INOUE Nagamu Keio University, 医学部, 講師 (00232546)
• Co-Investigator(Kenkyū-buntansha): OKAMOTO Susumu 慶應義塾大学, 医学部, 講師 (70255446) ; HISAMATSU Tadakazu 慶應義塾大学, 医学部, 講師 (60255437)
• Co-Investigator(Renkei-kenkyūsha): HIBI Toshifumi 慶應義塾大学, 医学部, 教授 (50129623) ; WATANABE Mamoru 東京医科歯科大学, 大学院・医歯学総合研究科器官システム制御学系消化器病態学, 教授 (10175127) ; MORIMOTO Chikao 東京大学, 医科学研究所先端医療研究センター免疫病態分野, 教授 (30119028)
• Project Period (FY): 2008 – 2010
• Keywords: 炎症性腸疾患 / 粘膜免疫 / 腸内細菌 / マクロファージ / クローン病

Research Abstract

We tried to elucidate the roles of macrophages in intestinal inflammation by using an IL-10-deficient (IL-10-/-) mouse colitis model, and demonstrated that abnormally differentiated subsets of intestinal macrophage play a key role in Th1-dominant chronic colitis through excess production of IL-12 and IL-23 in response to bacteria. Moreover, we found that lamina propria macrophages (LPMs) could be separated into two subsets with distinct side-scattered properties. LPM2 subset migrated in response to MCP-1 and produced a larger amount of IL-10 in response to commensal bacteria.

Research Products

• [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 40(9) Pages: 2409-2422
  • Peer Reviewed
• [Journal Article] Exacerbating role of gammadelta T cells in chronic colitis of T-cell receptor alpha mutant mice. (2008)
  • Author(s): Nanno M, Kanari Y, Naito T, Inoue N, Hisamatsu T, Chinen H, Sugimoto K, Shimomura Y, Yamagishi H, Shiohara T, Ueha S, Matsushima K, Suematsu M, Mizoguchi A, Hibi T, Bhan AK, Ishikawa
  • Journal Title: Gastroenterology 134(2) Pages: 481-490
  • Peer Reviewed
• [Journal Article] Non-pathogenic Escherichia coli strain Nissle 1917 inhibits signal transduction in intestinal epithelial cells. (2008)
  • Author(s): Kamada N, Maeda K, Inoue N, Hisamatsu T, Okamoto S, Hong KS, Yamada T, Watanabe N, Tsuchimoto K, Ogata H, Hibi T
  • Journal Title: Infect Immun 76(1) Pages: 214-220
  • Peer Reviewed
• [Journal Article] Imbalance in intestinal microflora constitution could be involved in the pathogenesis of inflammatory bowel disease. (2008)
  • Author(s): Takaishi H, Matsuki T, Nakazawa A, Takada T, Kado S, Asahara T, Kamada N, Sakuraba A, Yajima T, Higuchi H, Inoue N, Ogata H, Iwao Y, Nomoto K, Tanaka R, Hibi T
  • Journal Title: Int J Med Microbiol 298(5-6) Pages: 463-472
  • Peer Reviewed
• [Presentation] 腸管マクロファージからみたクローン病のサイトカインネットワーク異常 (2010)
  • Author(s): 久松理一、鎌田信彦、高山哲朗、齋藤理子、米野和明、松岡克善、岡本晋、井上詠、緒方晴彦、金井隆典、日比紀文
  • Organizer: 第47回日本消化器免疫学会総会、シンポジウム
  • Place of Presentation: 滋賀
  • Year and Date: 2010-07-09
• [Presentation] 胆汁酸はTGR5受容体を介してIL-12低産生型樹状細胞に分化誘導する/Bile acids generate IL-12 hypoproducingDCs via Tgr5 signaling pathway (2009)
  • Author(s): Saito R, Hisamatsu T, Takayama T, Kamada N, Ando S, Inoue N, Okamoto S, Kanai T, Hibi T
  • Organizer: 第39回日本免疫学会総会・学術集会、ワークショップ
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-02
• [Presentation] IL-10KOマウスにおけるマクロファージからのIL-12過剰産生機序の解明 (2009)
  • Author(s): 成瀬浩史、久松理一、鎌田信彦、岡本晋、井上詠、金井隆典、日比紀文
  • Organizer: 第46回日本消化器免疫学会、一般演題
  • Place of Presentation: 愛媛
  • Year and Date: 2009-07-23
• [Presentation] クローン病におけるCD14+腸管マクロファージの抗原提示能について (2009)
  • Author(s): 久松理一、鎌田信彦、本田治樹、北爪美奈、井上詠、岡本晋、金井隆典、日比紀文
  • Organizer: 第46回日本消化器免疫学会、シンポジウム
  • Place of Presentation: 愛媛
  • Year and Date: 2009-07-23
• [Presentation] クローン病における腸管マクロファージの腸内細菌認識異常 -IL-23を中心とした慢性炎症サイクル- (2008)
  • Author(s): 久松理一、鎌田信彦、小林拓、岡本晋、井上詠、緒方晴彦、金井隆典、日比紀文
  • Organizer: 第45回日本消化器免疫学会、シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2008-07-04
• [Presentation] MCP-1依存性腸管マクロファージサブセットの腸管免疫恒常性における役割 (2008)
  • Author(s): 高田康裕、久松理一、鎌田信彦、斎藤理子、高山哲朗、市川仁志、小林拓、知念寛、井上詠、岡本晋、日比紀文
  • Organizer: 第45回日本消化器免疫学会、一般演題
  • Place of Presentation: 京都
  • Year and Date: 2008-07-03
• [Remarks] ホームページ等 なし