Mechanism of abrogation of anergy in inflammatory bowel disease

2008 Fiscal Year Final Research Report

• Project/Area Number: 19590721
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Osaka University
• Principal Investigator: IIJIMA Hideki Osaka University, 医学系研究科, 助教 (90444520)
• Co-Investigator(Kenkyū-buntansha): TSUJII Masahiko 大阪大学, 医学系研究科, 講師 (40303937)
• Project Period (FY): 2007 – 2008
• Keywords: 消化器病学(食道、胃、小腸、大腸) / 炎症性腸疾患 / 免疫寛容 / 粘膜免疫

Research Abstract

炎症性腸疾患である潰瘍性大腸炎では、食事抗原や腸内細菌に対する免疫寛容の破綻が想定されている。炎症性腸疾患を自然発症するIL-10 ノックアウトマウスでは、免疫寛容を誘導すると言われているE3 ユビキチン・リガーゼが有意に低下しており、疾患の制御に重要な働きをしていることが示唆された。さらに、潰瘍性大腸炎患者の末梢血T リンパ球の解析により、免疫寛容関連ユビキチン・リガーゼが潰瘍性大腸炎患者の寛解の維持に重要であることが確認され、新たな治療標的となると考えられた

Research Products

• [Journal Article] Upregulation of GRAIL is Associated with Remission of Ulcerative Colitis (2008)
  • Author(s): Satoshi Egawa, Hideki Iijima, Shinzaki, S., Nakajima, S., Wang, J., Kondo, J., Ishii, S., Yoshio, T., Irie, T., Nishida, T., Kakiuchi, Y., Yasumaru, M., Yoshihara, H., Kanto, T., Tsujii, M., et.al.
  • Journal Title: Am J Physiol Gastrointest Liver Physiol 295 Pages: G163-G169
  • Peer Reviewed
• [Journal Article] IgG oligosaccharide alterations are a novel diagnostic marker for disease activity and the clinical course of inflammatory bowel disease (2008)
  • Author(s): Shinichiro Shinzaki, Hideki Iijima, et.al.
  • Journal Title: Am J Gastroenterol 103 Pages: 1173-81
  • Peer Reviewed
• [Journal Article] Topical Implantation of Mesenchymal Stem Cells has Beneficial Effects on Healing of Experimental Colitis in Rats (2008)
  • Author(s): Hayashi, Y., Tsuji, S.Tsujii, M., Nishida, T., Ishii, S., Iijima, H., et.al.
  • Journal Title: J Pharmacol Exp Ther 326 Pages: 523-31
  • Peer Reviewed
• [Journal Article] Topical transplantation of mesenchymal stem cells accelerates gastric ulcer healing in rats (2008)
  • Author(s): Hayashi, Y., Tsuji, S., Tsujii, M., Nishida, T., Ishii, S., Iijima, H., et.al.
  • Journal Title: Am J Physiol Gastrointest Liver Physiol 294 Pages: G778-786
  • Peer Reviewed
• [Journal Article] Cultured bone marrow cell local implantation accelerates healing of ulcers in mice (2008)
  • Author(s): Nishida, T., Tsuji, S., Tsujii, M., Ishii, S., Yoshio, T., Shinzaki, S., Egawa, S., Irie, T., Kakiuchi, Y., Yasumaru, M., Iijima, H., et.al.
  • Journal Title: J Gastroenterol 43 Pages: 124-135
  • Peer Reviewed
• [Journal Article] 他糖尿病におけるGERD : 定量的末梢知覚試験からの検討 (2008)
  • Author(s): 西田勉, 辻晋吾, 山本克己、飯島英樹
  • Journal Title: Progress in Medicine 28 Pages: 706-709
• [Journal Article] 抗TNFα抗体を用いた炎症性腸疾患の治療 (2008)
  • Author(s): 中島佐知子、飯島英樹
  • Journal Title: Clinician 574 Pages: 1195-1198
• [Journal Article] 他 CEA高値で発見された非症候性膵 (2008)
  • Author(s): 西田勉、山本克己、筒井秀作、疋田隼人、飯島英樹
  • Journal Title: グルカゴノーマの一例膵臓 23 Pages: 140-145
  • Peer Reviewed
• [Journal Article] Synergistic antitumor effects of celecoxib with 5-fluorouracil depend on IFN-gamma (2007)
  • Author(s): Irie, T., Tsujii, M., Tsuji, S., Yoshio, T., Ishii, S., Shinzaki, S., Egawa, S., Kakiuchi, Y., Nishida, T., Yasumaru, M., Iijima, H., et.al.
  • Journal Title: Int J Cancer 121 Pages: (4)878-83
  • Peer Reviewed
• [Presentation] Crohn病の診断と治療におけるダブルバル- ン小腸内視鏡の有用性 (2008)
  • Author(s): 近藤純平、飯島英樹、辻晋吾
  • Organizer: JDDW2008
  • Place of Presentation: 東京
  • Year and Date: 2008-10-03
• [Presentation] ビタミンK 欠乏と炎症性腸疾患活動性との関連について (2008)
  • Author(s): 中島佐知子、飯島英樹、林紀夫
  • Organizer: JDDW2008
  • Place of Presentation: 東京
  • Year and Date: 2008-10-03
• [Presentation] 他 クローン病術後に対する小腸内視鏡検査の有用性と問題点 (2008)
  • Author(s): 井上隆弘、飯島英樹
  • Organizer: JDDW2008
  • Place of Presentation: 東京
  • Year and Date: 2008-10-03
• [Presentation] 他マウス炎症性腸疾患におけるT 細胞の免疫寛容の関与についての検討 (2008)
  • Author(s): 柄川悟志、飯島英樹
  • Organizer: 第36回日本潰瘍学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2008-09-02
• [Presentation] Alterations in IgG fucosylated oligosaccharides are a novel diagnostic marker for disease activity and the clinical course of inflammatory bowel disease (2008)
  • Author(s): Shinzaki S, Iijima H, et.al.
  • Organizer: JHUPO conference 2008
  • Place of Presentation: 大阪
  • Year and Date: 2008-07-29
• [Presentation] 他潰瘍性大腸炎患者におけるT 細胞アナジーの検討 (2008)
  • Author(s): 柄川悟志、飯島英樹
  • Organizer: 第45回日本消化器免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-07-04
• [Presentation] Chemical intervention reverses oxidative stress-induced epigenetic alterations in colon cancer cells : Clues for new chemopreventive measures against aging and carcinogenesis (2008)
  • Author(s): Masahiko Tsujii, Shingo Tsuji, Hiroshi Eguchi, Shusaku Tsutsui, Hideki Iijima, et. al.
  • Organizer: Digestive disease week
  • Place of Presentation: San Diego, USA
  • Year and Date: 2008-05-21
• [Presentation] Agalactosyl IgG observed in inflammatory bowel disease is associated with enhancement of antibody-dependent phagocytosis in human monocytic cell line (2008)
  • Author(s): Hideki Iijima, et.al.
  • Organizer: Digestive disease week
  • Place of Presentation: San Diego, USA
  • Year and Date: 2008-05-20
• [Presentation] Upregulation of E3 ubiquitin ligases related to T cell anergy in CD4+ T cells isolated from patients with ulcerative colitis inremission (2008)
  • Author(s): Satoshi Egawa, Hideki Iijima, et.al.
  • Organizer: Digestive disease week
  • Place of Presentation: San Diego, USA
  • Year and Date: 2008-05-20
• [Presentation] Indications And Diagnostic Yield Of Double Balloon Enteroscopy In A Tertiary Care Setting : An Analysis Of 527 Cases With Suspected Small Bowel Diseases (2008)
  • Author(s): 10. Jumpei Kondo, Shingo Tsuji, Hideki Iijima, et.al.
  • Organizer: Digestive disease week
  • Place of Presentation: San Diego, USA
  • Year and Date: 2008-05-20
• [Presentation] Bone-marrow cells are able to develop Interstitial Cells of Cajal : Morphologic Evidences in W/Wv mice (2008)
  • Author(s): Shuji Ishii, Shingo Tsuji, Masahiko Tsujii, Jumpei Kondo, Sachiko Nakajima, Toshiyuki Yoshio, Shinichiro Shinzaki, Satoshi Egawa, Tsutomu Nishida, Yoshimi Kakiuchi, Kenji Watabe, Hideki Iijima, et.al.
  • Organizer: Digestive disease week
  • Place of Presentation: San Diego, USA
  • Year and Date: 2008-05-20
• [Presentation] Caldesmon suppresses cancer cell invasion by regulating podosome/invadopodium formation (2008)
  • Author(s): Toshiyuki Yoshio, Tsuyoshi Morita, Masahiko Tsujii, Jumpei Kondo, Sachiko Nakajima, Shuji Ishii, Shinichiro Shinzaki, Sato shi Egawa, Tsutomu Nishida, Yoshimi Kakiuchi, Hideki Iijima, et.al
  • Organizer: Digestive disease week
  • Place of Presentation: San Diego, USA
  • Year and Date: 2008-05-19
• [Presentation] Bone mineral density and biochemical markers of bone turnover in patients with inflammatory bowel disease (2008)
  • Author(s): Sachiko Nakajima, Hideki Iijima, et.al.
  • Organizer: Digestive disease week
  • Place of Presentation: San Diego, USA
  • Year and Date: 2008-05-19
• [Presentation] Possible roles of let-7 microRNA expression in the Cytotoxin-associated gene A (CagA) associated pathogenesis (2008)
  • Author(s): Jun Wang, Masahiko Tsujii, Shingo Tsuji, Toru Nakamura, Hiroshi Eguchi, Shusaku Tsutsui, Hideki Iijima, et.al.
  • Organizer: Digestive disease week
  • Place of Presentation: San Diego, USA
  • Year and Date: 2008-05-19
• [Presentation] Mesenchymal Stem Cells Transplantation Accelerates Gastric Ulcer Healing in Rats (2008)
  • Author(s): Yujiro Hayashi, Shingo Tsuji, Masahiko Tsujii, Tsutomu Nishida, Shuji Ishii, Hideki Iijima, et.al.
  • Organizer: Digestive disease week
  • Place of Presentation: San Diego, USA
  • Year and Date: 2008-05-18
• [Presentation] 炎症性腸疾患に見られるガラクトース欠損IgGによるマクロファージ機能への影響の解析 (2008)
  • Author(s): 飯島英樹, 他
  • Organizer: 第94回日本消化器病学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2008-05-08
• [Presentation] 林紀夫 骨髄移植モデルを用いた消化管運動障害の改善に関する検討 (2008)
  • Author(s): 石井修二、辻晋吾、辻井正彦、近藤純平、中島佐知子、由雄敏之、新崎信一郎、柄川悟志、西田勉、垣内佳美、渡部健二、飯島英樹
  • Organizer: 第94回日本消化器病学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2008-05-08
• [Presentation] 他Caldesmon はinvadopodium/podosomeの形成を阻害する癌細胞浸潤の抑制因子である (2008)
  • Author(s): 由雄敏之、森田剛、辻井正彦、近藤純平、中島佐知子、石井修二、新崎信一郎、柄川悟志、山本克己、渡部健二、西田勉、垣内佳美、飯島英樹
  • Organizer: 第94回日本消化器病学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2008-05-08
• [Presentation] 他 低用量アスピリンによる上部消化管粘膜障害 : 病変予測因子の検討 (2008)
  • Author(s): 垣内佳美、辻晋吾、辻井正彦、筒井秀作、飯島英樹
  • Organizer: 第94回日本消化器病学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2008-05-08
• [Presentation] 林紀夫炎症性腸疾患における免疫寛容分子GRAILの関与おけるIgG 糖鎖構造の変化ー血清マーカーとしての可能性 (2008)
  • Author(s): 新崎信一郎、飯島英樹
  • Organizer: 第94回日本消化器病学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2008-05-08
• [Presentation] 他 クローン病における悪性腫瘍合併症例の検討 (2008)
  • Author(s): 井上隆弘、飯島英樹
  • Organizer: 第94回日本消化器病学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2008-05-08
• [Presentation] 他マウス炎症性腸疾患におけるT 細胞の免疫寛容の関与についての検討 (2008)
  • Author(s): 柄川悟志、飯島英樹
  • Organizer: 第94回日本消化器病学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2008-05-08
• [Presentation] 他炎症性腸疾患患者における骨密度および骨代謝マーカーの検討 (2008)
  • Author(s): 中島佐知子、飯島英樹
  • Organizer: 第94回日本消化器病学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2008-05-08
• [Presentation] New diagnostic markier in Crohn's disease based on IgG oligosaccharideanalysis (2007)
  • Author(s): Shinichiro Shinzaki, Hideki Iijima, Takatoshi Nakagawa, Satoshi Egawa, Sachiko Nakajima, Jumpei Kondo, ShujiIshii, Tatsuya Kanto, Masahiko Tsujii, et.al
  • Organizer: The 2nd Korea-Japan IBD symposium
  • Place of Presentation: 東京
  • Year and Date: 2007-12-01
• [Presentation] Upregulation of GRAIL, an E3 ubiquitin ligase for induction of T cell anergy, in CD4+ Tcells of patients with ulcerative colitis in remission state (2007)
  • Author(s): Satoshi Egawa, Hideki Iijima, Masahiko Tsujii, et.al.
  • Organizer: 13th International congress of mucosal immunology
  • Place of Presentation: 東京
  • Year and Date: 2007-07-10
• [Presentation] New serologic marker for IBD based on the oligosaccharide analysis (2007)
  • Author(s): Shinichiro Shinzaki, Hideki Iijima, Takatoshi Nakagawa, Satoshi Egawa, Sachiko Nakajima, Tatsuya Kanto, Masahiko Tsujii, et.al.
  • Organizer: 13th International congress of mucosal immunology
  • Place of Presentation: 東京
  • Year and Date: 2007-07-10
• [Presentation] Expression of Grail, An E3 Ubiquitin Ligase for Induction of T Cell Anergy (2007)
  • Author(s): Satoshi Egawa, Hideki Iijima, Shinichiro Shinzaki, Sachiko Nakajima, Jumpei Kondou, Shuji Ishii, Toshiyuki Yoshio, Takanobu Irie, Yoshimi Kakiuchi, Tsutomu Nishida, Masakazu Yasumaru, Masahiko Tsujii, et.al
  • Organizer: in CD4+ T Cells of Patients with Ulcerative Colitis. DDW2007
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2007-05-17
• [Presentation] Cyclooxygenase-2 Regulates Toll-Like Receptor(TLR) 2 Expression and TLR2-Mediated Chemokine Production in Intestinal Epithelial Cells (2007)
  • Author(s): Shinichiro Shinzaki, Hideki Iijima, Satoshi Egawa, Sachiko Nakajima, Shuji Ishii, Toshiyuki Yoshio, Takanobu Irie, Yoshimi Kakiuchi, Tsutomu Nishida, Masakazu Yasumaru, Tatsuya Kanto, Masahiko Tsujii, et. al.
  • Organizer: DDW2007
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2007-05-17
• [Presentation] Transplantation of Bone Marrow-Derived Mesenchymal Stem Cells Ameliorated 2, 4, 6-Trinitrobenzene Sulfonic Acid (TNBS)-Induced Colitis in Rats (2007)
  • Author(s): Yujiro Hayashi, Shingo Tsuji, Masahiko Tsujii, Tsutomu Nishida, Shuji Ishii, Masato Komori, Takanobu Irie, Hideki Iijima, et.al.
  • Organizer: DDW2007
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2007-05-17
• [Presentation] Interferon-Gamma-Dependent Tumor-Suppressive Mechanisms of a COX-2 Inhibitor in Combination with 5-Fluorouracil. (2007)
  • Author(s): Takanobu Irie, Masahiko Tsujii, Shingo Tsuji, Toshiyuki Yoshio, Shuji Ishii, Shinichiro Shinzaki, Satoshi Egawa, Yoshimi Kakiuchi, Tsutomu Nishida, Masakazu Yasumaru, Hideki Iijima, et.al.
  • Organizer: DDW2007
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2007-05-17
• [Presentation] DNA Damage-Related Hypomethylation Induced Not Senescence Nor Apoptosis, But Aberrant Hypermethylation in CpG Island Methylator Phenotype-High Colon Cancer Cells Via Aberrant ERK / AKT Activation and Enhanced DNA Methyltransferase Activity (2007)
  • Author(s): Masahiko Tsujii, Shingo Tsuji, Shusaku Tsutsui, Hideki Iijima, et.al.
  • Organizer: DDW2007
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2007-05-17
• [Presentation] 他 潰瘍性大腸炎の緩解維持にT 細胞のアナジーが関与する (2007)
  • Author(s): 柄川悟志、飯島英樹、新崎信一郎、中島佐知子、考藤達哉、辻井正彦
  • Organizer: 第93回日本消化器病学会総会
  • Place of Presentation: 青森
  • Year and Date: 2007-04-19
• [Presentation] 林紀夫 レクチンを介した自然免疫系制御による炎症性腸疾患治療の可能性 (2007)
  • Author(s): 飯島英樹、新崎信一郎
  • Organizer: 第93回日本消化器病学会総会
  • Place of Presentation: 青森
  • Year and Date: 2007-04-19
• [Presentation] 他 糖鎖解析に基づく炎症性腸疾患の新たな血清マーカー (2007)
  • Author(s): 新崎信一郎、飯島英樹、中島佐知子、柄川悟志、考藤達哉、三善英知、辻井正彦
  • Organizer: 第93回日本消化器病学会総会
  • Place of Presentation: 青森
  • Year and Date: 2007-04-19
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/gh/index.Htm