Importance of dysregulated autophagy to intracellular parasiting bacteria in the pathogenesis of Crohn's disease

• Project/Area Number: 21590820
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Keio University
• Principal Investigator: INOUE Nagamu 慶應義塾大学, 医学部, 講師 (00232546)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• 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 / オートファジー / 自然免疫 / 細胞内寄生菌

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] 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, objective, multivariate biomarkers composed of plasma amino acid profiles for the diagnosis and assessment of inflammatory bowel disease (2012)
  • Author(s): Hisamatsu T, Inoue N, et al
  • Journal Title: PLoS One Volume: 7 Issue: 1 Pages: e31131-e31131
  • DOI: 10.1371/journal.pone.0031131
  • 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 T
  • Journal Title: J Gastroenterol Volume: 46(9) Pages: 1056-63
  • NAID: 10029706720
  • 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, Inoue N, et al
  • Journal Title: J Gastroenterol Volume: 46 Issue: 9 Pages: 1056-1063
  • DOI: 10.1007/s00535-011-0425-7
  • NAID: 10029706720
  • 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: 2409-2422
  • Peer Reviewed
• [Journal Article] 消化器疾患と樹状細胞 病態の解明と治療法の開発 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 (2010)
  • Author(s): 久松理一、井上詠, 他
  • Journal Title: 消化器と免疫 Volume: 46 Pages: 36-38
• [Journal Article] 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 (2009)
  • Author(s): 久松理一, 井上詠, 他
  • Journal Title: 消化器と免疫 45 Pages: 52-54
• [Presentation] Intestinal CXCR4+IgG+immature plasma cells contribute to the pathogenesis of ulcerative colitis through IgGImmune complex-Fc_YR signaling (2011)
  • Author(s): Hisamatsu T, Inoue N, et al
  • Organizer: 15th International Congress of Mucosal Immunology
  • Place of Presentation: Paris, France
  • Year and Date: 2011-07-07
• [Presentation] Intestinal CXCR4+IgG+immature plasma cells contribute to the pathogenesis of ulcerative colitis through IgG Immune complex-FcγR signaling (2011)
  • Author(s): Hisamatsu T, Uo M, Miyoshi J, Yoneno K, Inoue N, Ogata H, Kanai T, Hibi T
  • Organizer: 15^<th> International Congress of Mucosal Immunology
  • Place of Presentation: Paris, France
• [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、井上詠, 他
  • Organizer: 第47回日本消化器免疫学会総会
  • Place of Presentation: 大津
  • Year and Date: 2010-07-09
• [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
• [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, 井上詠, 他
  • Organizer: 第46回日本消化器免疫学会総会
  • Place of Presentation: 松山
  • Year and Date: 2009-07-23
• [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 hypoproducing DCs 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
• [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
• [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
  • Place of Presentation: 愛媛