T-cell costimulation-mediated regulation of mucosal inflammation

• Project/Area Number: 21390114
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Tohoku University
• Principal Investigator: ISHII Naoto 東北大学, 大学院・医学系研究科, 教授 (60291267)
• Co-Investigator(Kenkyū-buntansha): ONO Masao 東北大学, 大学院・医学系研究科, 教授 (20302218) ; KINOUCHI Yoshitaka 東北大学, 大学院・医学系研究科, 准教授 (20250780)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2011: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2010: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2009: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: 炎症性腸疾患 / 疾患感受性遺伝子 / 遺伝子導入マウス

Research Abstract

We examined a quantitative trait locus (QTL)that may make C57BL/6 (B6)mice susceptible and BALB/c mice resistant to IBD developing in OX40 ligand-transgenic (OX40L-Tg)mice. The locus exhibits highly significant logarithm of odd (LOD)score for the IBD severi ty. Further positional mapping performed using single nucleotide polymorphisms (SNPs)at this locus revealed the lowest p-value (<10-7 )for the SNP in TNFRSF14 gene. TNFRSF14 encodes the herpes virus entry mediator (HVEM), which belongs to the TNF recepto r superfamily.

Research Products

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