T細胞共刺激分子を標的とした炎症性腸疾患発症制御

• 研究課題/領域番号: 21390114
• 研究種目: 基盤研究(B)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 実験病理学
• 研究機関: 東北大学
• 研究代表者: 石井 直人 東北大学, 大学院・医学系研究科, 教授 (60291267)
• 研究分担者: 小野 栄夫 東北大学, 大学院・医学系研究科, 教授 (20302218) ; 木内 喜孝 東北大学, 大学院・医学系研究科, 准教授 (20250780)
• 研究期間 (年度): 2009 – 2011
• 研究課題ステータス: 完了 (2011年度)
• 配分額: 18,590千円 (直接経費: 14,300千円、間接経費: 4,290千円); 2011年度: 5,330千円 (直接経費: 4,100千円、間接経費: 1,230千円); 2010年度: 5,330千円 (直接経費: 4,100千円、間接経費: 1,230千円); 2009年度: 7,930千円 (直接経費: 6,100千円、間接経費: 1,830千円)
• キーワード: 炎症性腸疾患 / 疾患感受性遺伝子 / 遺伝子導入マウス

研究概要

我々は、自身が開発した炎症性腸疾患(IBD)自然発症マウスがC57BL/6系統依存的にIBDを発症することを利用して、マウスIBD感受性遺伝子の同定を試みた。感受性遺伝子を同定するために、疾患感受性系統(C57B/6)と疾患抵抗性系統(BALB/c)をOX40L-Tg背景下に交配し、IBD重症度を指標として遺伝子連鎖解析等の種々の解析を行った。その結果, 有力な候補遺伝子HVEMを同定した。

研究成果

• [雑誌論文] Development of a multi-step leukemogenesis model of MLL-rearranged leukemia using humanized mice (2012)
  • 著者名/発表者名: Moriya K, Suzuki M, Watanabe Y, Takahashi T, Aoki Y, Uchiyama T, Kumaki S, Sasahara Y, Minegishi M, Kure S, Tsuchiya S, Sugamura K, and Ishii N.
  • 雑誌名: PLoS ONE 巻: (in press)
• [雑誌論文] Runx1-deficiency in CD4+ T cells causes fatal autoimmune inflammatory lung disease due to spontaneous hyperactivation of cells (2012)
  • 著者名/発表者名: Wong WF, Kohu K, Nakamura A, Ebina M, Kikuchi T, Tazawa R, Tanaka K, Kon S, Funaki T, Sugahara-Tobinai A, Looi CY, Endo S, Funayama R, Kurokawa M, Habu S, Ishii N, Fukumoto M, Nakata K, Takai T, and Satake M.
  • 雑誌名: J. Immunol 巻: (in press)
• [雑誌論文] nduction of human humoral immune responses in a novel HLA-DR-expressing transgenic NOD/Shi-scid/γcnull mouse (2012)
  • 著者名/発表者名: Suzuki M, Takahashi T, Katano I, Ito R, Ito M, Harigae H, Ishii N, and Sugamura K.
  • 雑誌名: Int. Immunol 巻: 24 ページ: 243-252
• [雑誌論文] Induction of human humoral immune responses in a novel HLA-DR-expressing transgenic NOD/Shi-scid/γc^<null> mouse (2012)
  • 著者名/発表者名: Suzuki M, Takahashi T, Katano I, Ito R, Ito M, Harigae H, Ishii N, Sugamura K.
  • 雑誌名: Int Immunol 巻: 24 号: 4 ページ: 243-52
  • DOI: 10.1093/intimm/dxs045
  • 査読あり
• [雑誌論文] ndispensable roles of OX40L-derived signal and epistatic genetic effect in immune-mediated pathogenesis of spontaneous pulmonary hypertension (2011)
  • 著者名/発表者名: Rabieyousefi M, Soroosh P, Satoh K, Date F, Ishii N, Yamashita M, Oka M, McMurtry IF, Shimokawa H, Nose M, Sugamura K, and Ono M.
  • 雑誌名: BMC Immunol 巻: 12 ページ: 67-67
• [雑誌論文] Interaction between NK cells and dendritic cells generate MHC class II-dressed NK cells to regulate CD4+ T cells (2011)
  • 著者名/発表者名: Nakayama M, Takeda K, Kawano M, Takai T, Ishii N, and Ogasawara K.
  • 雑誌名: Proc Natl. Acad. Sci. USA 巻: 108 ページ: 18360-5
• [雑誌論文] Involvement of osteopontin and its signaling molecule CD44 in clinicopathological features of adult T cell leukemia (2011)
  • 著者名/発表者名: Chagan-Yasutan H, Tsukasaki K, Takahashi Y, Oguma S, Harigae H, Ishii N, Zhang J, Fukumoto M, and Hattori T.
  • 雑誌名: Leuk Res 巻: 35 ページ: 1484-90
• [雑誌論文] A genome-wide association study identifies RNF213 as the first Moyamoya disease gene (2011)
  • 著者名/発表者名: Kamada, F., Aoki, Y., Narisawa, A., Abe, Y., Komatsuzaki, S., Kikuchi, A., Kanno, J., Niihori, T., Ono, M., Ishii, N., Owada, Y., Fujimura, M., Mashimo, Y., Suzuki, Y., Hata, A., Tsuchiya, S, Tominaga, T., Matsubara, Y, and Kure, S.
  • 雑誌名: J. Hum. Genet 巻: 56 ページ: 34-40
  • NAID: 10030657293
• [雑誌論文] Indispensable roles of OX40L-derived signal and epistatic genetic effect in immune-mediated pathogenesis of spontaneous pulmonary hypertension (2011)
  • 著者名/発表者名: Rabieyousefi M, Soroosh P, Satoh K, Date F, Ishii N, Yamashita M, Oka M,McMurtry IF, Shimokawa H, Nose M, Sugamura K, Ono M.
  • 雑誌名: Immunol 巻: 12 号: 1 ページ: 67-67
  • DOI: 10.1186/1471-2172-12-67
  • 査読あり
• [雑誌論文] Interaction between NK cells and dendritic cells generate MHC class II-dressed NK cells to regulate CD4^+ T cells (2011)
  • 著者名/発表者名: Nakayama M, et al
  • 雑誌名: Proc.Natl.Acad.Sci.USA 巻: 108 号: 45 ページ: 18360-18365
  • DOI: 10.1073/pnas.1110584108
  • 査読あり
• [雑誌論文] Involvement of osteopontin and its signaling molecule CD44 in clinicopathological features of adult T cell leukemia (2011)
  • 著者名/発表者名: Chagan-Yasutan H, Tsukasaki K, Takahashi Y, Oguma S, Harigae H, Ishii N, Zhang J, Fukumoto M, Hattori T.
  • 雑誌名: Leuk Res. 巻: 35 号: 11 ページ: 1484-90
  • DOI: 10.1016/j.leukres.2011.05.011
  • 査読あり
• [雑誌論文] OX40 ligand plays an important role in the development of atherosclerosis through vasa vasorum neovascularizatio (2010)
  • 著者名/発表者名: Nakano, M., Fukumoto, Y., Satoh, K., Ito, Y., Kagaya, Y., Ishii N., Sugamura, K., and Shimokawa, H.
  • 雑誌名: Cardiovasc. Res 巻: 88 ページ: 539-546
• [雑誌論文] Characterization of the EpCAM+ cell population in hepatocellular carcinoma cell lines (2010)
  • 著者名/発表者名: Kimura, O., Takahashi, T., Ishii N, Inoue, Y., Ueno, Y., Kogure, T., Fukushima, K., Shiina, M., Yamagiwa, Y., Kondo, Y., Inoue, J., Kakazu, E., Iwasaki, T., Kawagishi, N., Shimosegawa, T., and Sugamura, K
  • 雑誌名: Cancer Sci 巻: 101 ページ: 2145-2155
• [雑誌論文] In vivo assay of human NK-dependent ADCC using NOD/SCID/γcnull (NOG)mice (2010)
  • 著者名/発表者名: Shiokawa, M., Takahashi, T., Murakami, A., Kita, S, Ito, M., Sugamura, K., and Ishii, N.
  • 雑誌名: Biochem. Biophys. Res. Commun 巻: 399 ページ: 733-737
• [雑誌論文] Regulatory T cells are necessary for implantation and maintenance of early pregnancy but not late pregnancy in allogeneic mice (2010)
  • 著者名/発表者名: Shima, T., Sasaki, Y., Itoh, M., Nakashima, A., Ishii N., Sugamura, K., and Saito, S.
  • 雑誌名: J. Reprod. Immunol 巻: 85 ページ: 121-129
• [雑誌論文] OX40-OX40L ligand interaction in T cell-mediated immunity and immunopathology (2010)
  • 著者名/発表者名: Ishii, N., Takahashi, T., Soroosh, P., and Sugamura, K.
  • 雑誌名: Adv. Immunol 巻: 105 ページ: 63-98
• [雑誌論文] Serial OX40 engagement on CD4+ T cells and NKT cells causes allergic airway inflammation (2010)
  • 著者名/発表者名: Damayanti T, Kikuchi T, Zaini J, Daito H, Kanehira M, Kohu K, Ishii N, Satake M, Sugamura K, and Nukiwa T.
  • 雑誌名: Am. J. Respir. Crit. Care. Med 巻: 181 ページ: 688-698
• [雑誌論文] Early production of tumor necrosis factor-alpha by Gr-1(+)cells and its role in the host defense to pneumococcal infection in lungs (2010)
  • 著者名/発表者名: Hatta, M., Yamamoto, N., Miyazato, A., Ishii, N., Nakamura, K., Inden, K., Aoyagi, T., Kunishima, H., Hirakata, Y., Suzuki, K., Kaku, M., and Kawakami, K.
  • 雑誌名: FEMS Immunol & Medical Microbiol 巻: 58 ページ: 182-192
• [雑誌論文] OX40-OX40L interaction in T cell-mediated immunity and immunopathology (2010)
  • 著者名/発表者名: Ishii N, et al
  • 雑誌名: Adv.Immunol. 巻: 105 ページ: 63-98
  • 査読あり
• [雑誌論文] Serial OX40 engagement on CD4^+ T cells and NKT cells causes allergic airway inflammation (2010)
  • 著者名/発表者名: Damayanti, T, et al
  • 雑誌名: Am.J.Respir.Crit.Care.Med 巻: 181 ページ: 688-698
  • 査読あり
• [雑誌論文] OX40 ligand plays an important role in the development of atheroscleros is through vasa vasorum neovascularization. (2010)
  • 著者名/発表者名: Nakano, M., et al
  • 雑誌名: Cardiovasc.Res. 巻: 88 ページ: 539-546
  • 査読あり
• [雑誌論文] Characterization of the EpCAM^+ cell population in hepatocellular care inoma cell lines. (2010)
  • 著者名/発表者名: Kimura O, et al
  • 雑誌名: Cancer Sci. 巻: 101 ページ: 2145-2155
  • 査読あり
• [雑誌論文] OX40-OX40L ligand interaction in T cell-mediated immunity and immunopathology (2010)
  • 著者名/発表者名: Naoto Ishii
  • 雑誌名: Adv.Immunol. 105(印刷中)
  • 査読あり
• [雑誌論文] Serial OX40 engagement on CD4^+ T cells and NKT cells causes allergic airway inflammation (2010)
  • 著者名/発表者名: Damayanti, T
  • 雑誌名: Am.J.Respir.Crit.Care.Med 181 ページ: 688-698
  • 査読あり
• [雑誌論文] Early production of tumor necrosis factor-alpha by Gr-1(+) cells and its role in the host defense to pneumococcal infection in lungs. (2010)
  • 著者名/発表者名: Hatta, M.
  • 雑誌名: FEMS Immunol & Medical Microbiol 58 ページ: 182-192
  • 査読あり
• [雑誌論文] The analysis of the functions of human B and T cells in humanized NOD/shi-scid/γc^<null>(NOG)mice(hu-HSC NOG mice) (2010)
  • 著者名/発表者名: Watanabe, Y
  • 雑誌名: Int.Immunol. 21 ページ: 843-858
  • 査読あり
• [雑誌論文] The analysis of the functions of human B and T cells in humanized NOD/shi-scid/γcnull (NOG)mice (hu-HSC NOG mice) (2009)
  • 著者名/発表者名: Watanabe, Y., Takahashi, T., Okajima, A., Shiokawa, M., Ishii, N., Katano, I., Ito, R., Ito, M., Minegishi, M., Minegishi, N., Tsuchiya, S., and Sugamura, K.
  • 雑誌名: Int. Immunol 巻: 21 ページ: 843-858
• [雑誌論文] Statin ameliorates hypoxia-induced pulmonary hypertension associated with down-regulated stromal cell-derived factor-1 (2009)
  • 著者名/発表者名: Satoh, K., Fukumoto, Y., Nakano, M., Sugimura, K., Nawata, J., Demachi, J., Karibe, A., Kagaya, Y., Ishii, N., Sugamura, K., and Shimokawa, H.
  • 雑誌名: Cardiovasc. Res 巻: 81 ページ: 226-34
• [学会発表] OX40 contributes to the generation and maintenance of memory CD4+T cells (2011)
  • 著者名/発表者名: Ishii N
  • 学会等名: 第40回日本免疫学会学術集会・国際シンポジウム
  • 発表場所: 千葉市
  • 年月日: 2011-11-29
• [学会発表] OX40 contributes to the generation and maintenance of memory CD4+ T cells (2011)
  • 著者名/発表者名: Ishii N
  • 学会等名: 40th JSI international symposium
  • 発表場所: Chiba
• [学会発表] Positional identification of TNFRSF14, encoding the herpes virus entry mediator, as a susceptibility gene for inflammatory bowel disease in mice (2010)
  • 著者名/発表者名: Kawabe T, Irie M, Ono M, Asao A, Zhang M, Yoshida A, Takahashi T, Uede T, Watanabe N, Sugamura K, and Ishii N.
  • 学会等名: 14th International Congress of Immunology
  • 発表場所: Kobe, Japan
• [学会発表] OX40-Mediated Susceptibility to Leishmania major Infection is Dependent on IL-13 (2010)
  • 著者名/発表者名: Asao A, Ndhlovu LC, Hoshino T, Sugamura K, and Ishii N.
  • 学会等名: 14th International Congress of Immunology
  • 発表場所: Kobe, Japan
• [学会発表] The analysis of the functions of human T cells in humanized NOD/shi-scid/gamma cnull (NOG)-HLA transgenic mice (2010)
  • 著者名/発表者名: Takahashi T, Suzuki M, Katano I, Ito R, Ishii N, Ito M, and Sugamura K.
  • 学会等名: 14th International Congress of Immunology (ICI2010)
  • 発表場所: Kobe, Japan
• [学会発表] Roles of OX40 in the generation and maintenance of memory T cells (2009)
  • 著者名/発表者名: Naoto Ishii
  • 学会等名: The first CSI/JSI/KAI joint symposium on Immunology
  • 発表場所: Shanghai, China
• [学会発表] Roles of OX40 in the generation and maintenance of memory T cells (2009)
  • 著者名/発表者名: Naoto Ishii
  • 学会等名: 3rd NM-GCOE international symposium
  • 発表場所: Sendai
• [学会発表] (2009)
  • 著者名/発表者名: Asao A, Sugamura K, and Ishii N
  • 学会等名: 3rd NM-GCOE international symposium
  • 発表場所: Sendai
• [学会発表] Roles of OX40 in the generation and maintenance of memory T cells (2009)
  • 著者名/発表者名: Naoto Ishii
  • 学会等名: 1^<st> International CSI/JSI/KAI Joint Symposium on Immunology
  • 発表場所: Shanghai, China
• [備考]
  • URL: http://www.immunol.med.tohoku.ac.jp//index.html