The functional analysis of IL-7 receptor in colitogenic memory Tcell.

• Project/Area Number: 22590695
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: OKADA Eriko 東京医科歯科大学, 医学部附属病院, 助教 (20376784)
• Co-Investigator(Kenkyū-buntansha): NEMOTO Yasuhiro 東京医科歯科大学, 大学院・医歯学総合研究科, 助教 (20456213) ; WATANABE Mamoru 東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (10175127)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: IL-7 / IL-7R / メモリーT細胞 / 炎症性腸疾患

Research Abstract

As the final goal for the development of epoch-making radical treatment to inflammatory bowel disease (IBD), we have focused "colitogenic memory T cell" that continues being underlying in the body throughout the life. We have then proved the importance of the IL-7/IL-7 receptor (IL-7R) signal in the mechanism for the maintenance of colitogenic memory T cell and the importance of IL-7R signaling in colitis model. IL-7Rα was expressed in CD4+T cell in both normal mouse and colitis mouse. And the expression of IL-7Rα was up-regulated in the CD4+T cell with the onset of the colitis. These results suggested that IL-7/IL-7R signal in the CD4+T cell might be novel target for the therapy of the inflammatory bowel diseases.

Research Products

• [Journal Article] Modifiedsingle-operator method for double-balloon endoscopy (2012)
  • Author(s): Araki A, Suzuki S, Tsuchiya K, OshimaS, Okada E, Watanabe M
  • Journal Title: Dig Endosc Volume: 24(6) Issue: 6 Pages: 470-4
  • DOI: 10.1111/j.1443-1661.2012.01321.x
  • Peer Reviewed
• [Journal Article] Endoscopic ultrasound with double-balloon endoscopy for the diagnosis of inverted Meckel'sdiverticulum: a case report (2012)
  • Author(s): Araki A, Tsuchiya K, Oshima S, Okada E,Suzuki S, Akiyama JM, Fujii T, OkamotoR, Watanabe M
  • Journal Title: J Med Case Rep Volume: 6(1) Issue: 1 Pages: 328-328
  • DOI: 10.1186/1752-1947-6-328
  • Peer Reviewed
• [Journal Article] Histological Diagnosis ofFollicular Lymphoma by Biopsy of SmallIntestinal Normal Mucosa (2012)
  • Author(s): Okada E, Araki A, Suzuki S, Watanabe H, Ikeda T, Watanabe T, Kurata M, EishiY, Watanabe M
  • Journal Title: Dig Endosc Volume: in press Issue: 5 Pages: 22-22
  • DOI: 10.1111/j.1443-1661.2012.01386.x
  • Peer Reviewed
• [Journal Article] Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5+stem cell (2012)
  • Author(s): Yui S, Nakamura T, Sato T, Nemoto Y, Mizutani T, Zheng X, Ichinose S, Nagaishi T, Okamoto R, Tsuchiya K, Clevers H, and Watanabe M
  • Journal Title: Nature Medicine Volume: 18 Issue: 4 Pages: 618-623
  • DOI: 10.1038/nm.2695
  • Peer Reviewed
• [Journal Article] Real-time analysis of P-glycoprotein-mediated drug transport across primary intestinal epithelium three-dimensionally cultured in vitro (2012)
  • Author(s): Mizutani T, Nakamura T, et al
  • Journal Title: Biochem Biophys Res Commun Volume: 419 Issue: 2 Pages: 238-243
  • DOI: 10.1016/j.bbrc.2012.01.155
  • Peer Reviewed
• [Journal Article] The development of colitogenic CD4+ T cells is regulated by IL-7 in collaboration with natural killer cell function in a murine model of colitis (2012)
  • Author(s): Yamaji O, Totsuka T
  • Journal Title: J Immunol Volume: 188 Issue: 6 Pages: 2524-2536
  • DOI: 10.4049/jimmunol.1100371
  • Peer Reviewed
• [Journal Article] MR enterocolonography is useful for simultaneous evaluation of small and large intestinal lesions in Crohn's disease (2011)
  • Author(s): Hyun SB, Kitazume Y, Suzuki S, Watanabe M, et al
  • Journal Title: Inflam Bowel Dis Volume: 17 Issue: 5 Pages: 1063-1072
  • DOI: 10.1002/ibd.21510
  • Peer Reviewed
• [Journal Article] Longitudinal cell formation in the entire human small intestine is correlated with the localization of Hath1 and Klf4 (2011)
  • Author(s): Iwasaki M, Tsuchiya K, Suzuki S, Watanabe M, et al
  • Journal Title: J Gastroenterol Volume: 46 Issue: 2 Pages: 191-202
  • DOI: 10.1007/s00535-010-0346-x
  • NAID: 10029027237
  • Peer Reviewed
• [Journal Article] Luminal CD4+ T cells penetrate gut epithelial monolayers and egress from lamina propria to blood circulation (2011)
  • Author(s): Nemoto Y, Watanabe M
  • Journal Title: Gastroenterology Volume: 141 Issue: 6 Pages: 2130-2139
  • DOI: 10.1053/j.gastro.2011.08.035
  • Peer Reviewed
• [Journal Article] Upregulated IL-7Rα expression on colitogenic memory CD4+ T cells may participate in the development and persistence of chronic colitis (2011)
  • Author(s): Shinohara, T., et al
  • Journal Title: J.Immunol. Volume: 186 Issue: 4 Pages: 2623-2632
  • DOI: 10.4049/jimmunol.1000057
  • Peer Reviewed
• [Journal Article] Suppression of Hath1 gene expression directly regulated by Heslvia Notch signaling is associated with goblet cell depletion in ulcerative colitis (2011)
  • Author(s): Zheng X, Nakamura T, et al
  • Journal Title: Inflamm Bowel Dis Volume: 17 Issue: 11 Pages: 2251-2260
  • DOI: 10.1002/ibd.21611
  • Peer Reviewed
• [Journal Article] Upregulated IL-7 receptor (alpha) expression on colitogenic memory CD4+ T cells may participate in the development and persistence of chronic colitis. (2011)
  • Author(s): Shinohara T, Nemoto Y, et al.
  • Journal Title: The Journal of Immunology Volume: 186 Pages: 2623-32
  • Peer Reviewed
• [Journal Article] IL-2 is positively involved in the development of colitogenic CD4+ IL-7R alpha high memory T cells in chronic colitis. (2010)
  • Author(s): Kameyama K, Nemoto Y, et al
  • Journal Title: European Journal of Immunology Volume: 40 Pages: 2423-36
  • Peer Reviewed
• [Journal Article] MR enterocolonography is useful for simultaneous evaluation of small and large intestinal lesions in Crohn's disease. (2010)
  • Author(s): Hyun SB, Kitazume Y, Nagahori M, Okada E, Watanabe M
  • Journal Title: Inflam Bowel Dis Volume: in press
  • Peer Reviewed
• [Journal Article] Longitudinal cell formation in the entire human small intestine is correlated with the localization of Hathl and Klf4. (2010)
  • Author(s): Iwasaki M, Tsuchiya K, Okamoto R, Okada E, Watanabe M
  • Journal Title: J Gastroenterol Volume: in press
  • Peer Reviewed
• [Presentation] Epithelial regeneration by cultured colonic cells expanded from a single adult Lgr5+ stem cell (2012)
  • Author(s): Nakamura T, Watanabe M
  • Organizer: The 6th Korea-Japan IBD Symposium
  • Place of Presentation: Tokyo
  • Year and Date: 2012-01-28
• [Presentation] 炎症性腸疾患病原性メモリーCD4^+ T細胞は腸管粘膜から全身血流に再循環する (2011)
  • Author(s): 根本泰宏
  • Organizer: JDDW2011
  • Place of Presentation: 福岡
  • Year and Date: 2011-10-21
• [Presentation] ダブルバルーン内視鏡を用いた潰瘍性大腸炎患者の小腸所見の検討 (2011)
  • Author(s): 岡田英理子
  • Organizer: 第81回日本消化器内視鏡学会総会
  • Year and Date: 2011-08-18
• [Presentation] 炎症性腸疾患難治性の要因としての腸炎惹起性メモリーCD4^+ T細胞再循環機構 (2011)
  • Author(s): 根本泰宏
  • Organizer: 日本消化器免疫学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2011-07-21
• [Presentation] Luminal CD4^+ T cells penetrate gut epithelial monolayers and egress from lamina propria to blood circulation (2011)
  • Author(s): 根本泰宏
  • Organizer: ICMI
  • Place of Presentation: Paris
  • Year and Date: 2011-07-07
• [Presentation] 炎症性腸疾患メモリーCD4^+ T細胞の腸管-骨髄循環経路 (2011)
  • Author(s): 根本泰宏
  • Organizer: 第35回日本リンパ学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-03
• [Presentation] CD4^+CD45RB^<high>T細胞移入大腸炎マウスの病態における腸内細菌の役割 (2011)
  • Author(s): 根本泰宏
  • Organizer: 日本消化器病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-13
• [Presentation] IL-7Rα expression on CD4^+ T cells, but not on other cells is essential for the development of chronic colitis (2011)
  • Author(s): 根本泰宏
  • Organizer: DDW2011
  • Place of Presentation: シカゴ
  • Year and Date: 2011-05-10
• [Presentation] Regeneration of Damaged Colonic Tissue by Transplantation of Colonic Epithelial Stem Cells Maintained and Expanded In Vitro (2011)
  • Author(s): Yui S, Nakamura T, Watanabe M, et al
  • Organizer: DDW2011
  • Place of Presentation: Chicago
  • Year and Date: 2011-05-07
• [Presentation] 腸炎惹起性メモリーCD4+T細胞再循環経路をターゲットとした炎症性腸疾患の治療戦略 (2010)
  • Author(s): 根本泰宏
  • Organizer: JDDW 2011(日本消化器病関連週間)
  • Place of Presentation: 横浜
  • Year and Date: 2010-10-14
• [Presentation] IL-7-producing mesenchymal stromal cells sustain colitogenic memory CD4+ Tcells for the persistence of inflammatory bowel disease (2010)
  • Author(s): Nemoto T
  • Organizer: 国際免疫学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-25
• [Presentation] 炎症性腸疾患メモリーCD4+T細胞は腸内細菌非依存的/IL-7依存的に維持される (2010)
  • Author(s): 根本泰宏
  • Organizer: 日本消化器免疫学会総会
  • Place of Presentation: 滋賀
  • Year and Date: 2010-07-09
• [Presentation] IL-7-producing mesenchymal stem cells sustain colitogenic memory CD4+ Tcells for the persistence of chronic colitis (2010)
  • Author(s): Nemoto T
  • Organizer: DDW 2010(米国消化器病関連週間)
  • Place of Presentation: 米国(ニューオリンズ)
  • Year and Date: 2010-05-02
• [Presentation] ダブルバルーン内視鏡の一人法 新しい挿入方法 Hooking Tecnique
  • Author(s): 荒木昭博、岡田英理子、鈴木伸治、新田沙由梨、藤井俊光、大塚和朗、渡辺守
  • Organizer: 第99回 日本消化器病学会
  • Place of Presentation: かごしま県民交流センター（鹿児島）
• [Book] 実験医学増刊号:免疫記憶の制御と疾患治療 (2011)
  • Author(s): 根本泰宏、金井孝典、渡辺守
  • Total Pages: 7
  • Publisher: 羊土社
• [Patent(Industrial Property Rights)] 大腸上皮幹細胞の単離・培養技術とこれを用いた大腸上皮移植技術 (2011)
  • Inventor(s): 渡辺守・中村哲也
  • Industrial Property Rights Holder: 国立大学法人東京医科歯科大学
  • Industrial Property Number: 2011-236469
  • Filing Date: 2011-10-27