• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2007 Fiscal Year Final Research Report Summary

Establishment of the system to control T lymphocyte functions using Notch ligands

Research Project

Project/Area Number 18590474
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionThe University of Tokushima

Principal Investigator

KISHIHARA Kenji  The University of Tokushima, Institute of Health Biosciences, Graduate School, Associate Professor (80214774)

Project Period (FY) 2006 – 2007
KeywordsNotch / Notch ligands / T lymphocyte / immunoregulation / Lunatic fringe / Glycosylation / NK cell
Research Abstract

In this research project, the first attempt to establish the system to control T lymphocyte function was done using tail-truncated Notch ligands because such mutanted molecules modulate fruit fly development. Unfortunately, the attempt was failed despite various constructs of tail-truncated Notch ligand genes were produced and then assayed. Nextly, the following two projects were performed : (1) to study a role of lunatic fringe, which modulate Notch-signaling by glycosylation of Notch molecules, in T cell development and (2) to examine effects of Notch/Notch ligands on NK cell activation and fuction.
(1)Overexpression of Lfng in Jurkat T cells strengthened Notch signaling, indicating that Lfng is a positive regulator for Notch signaling in T cells. The enforced expression of Lfng in thymocytes enhanced the development of immature CD8SP cells but decreased mature CD4SP and CD8SP cells. In contrast, the down-regulation of Lfng in thymocytes suppressed DP cell development due to the defec … More tive diffentiation in DN cell stage. The overexpression of Lfng in fetal liver-derived hemopoietic stem cells enhanced T cell development, whereas its down-regulation suppressed it. These results suggest that the high expression of Ling in DN cells contributes to enhance T cell differentiation through strengthening Notch signaling.
(2)Enforced expression of Jagged2 on A20 tumor cells suppressed their growth in vivo, which was abrogated by depleting NK cells. Consistently, coinoculation of A20 cells with DC overexpressing Jagged2suppressed the growth of A20 cells in mice. Stimulation of NK cells with Jagged2 directly enhanced their cytotoxicity, IFN-gamma production, and proliferation. Ligation of Notch2 on MC cells enhanced their cytotoxic activity, which was suppressed by a gamma-secretase inhibitor. These results indicate that the Jagged2-Notch axis plays a crucial role in DC-mediated MC cell cytotoxicity. Furthermore, manipulation of this interaction may provide an approach to induce potent tumor immunity.sp Less

  • Research Products

    (6 results)

All 2008 2007 2006 0

All Journal Article (4 results) (of which Peer Reviewed: 2 results) Presentation (2 results)

  • [Journal Article] Dendritic cell-mediated NK cell activation is controlled by Jagged2-Notch interaction2008

    • Author(s)
      Mika Kijima, et. al.
    • Journal Title

      Proceedings of the National Academy of Sciences of the USA (PNAS) 105

      Pages: 7010-7015

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Dendritic cell-mediated NK cell activation is controlled by Jagged2-Notch interaction2008

    • Author(s)
      Mika, Kijima, et. al.
    • Journal Title

      Proceedings of the National Academy of Sciences of the USA 105-19

      Pages: 7010-7015

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Lunatic fringe controls T cell differentiation through modulating Notch signaling2006

    • Author(s)
      Shin-ichi Tsukumo, et. al.
    • Journal Title

      The Journal of Immunology 177

      Pages: 8365-8371

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Lunatic fringe controls T cell differentiation through modulating Notch signaling2006

    • Author(s)
      Shin-ichi, Tsukumo, et. al.
    • Journal Title

      The Journal of Immunology 177-12

      Pages: 8365-83712

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Jagged2によるNK細胞活性化制御の解析2007

    • Author(s)
      Mika Kijima, 等
    • Organizer
      第37回日本免疫学会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-21
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Jagged2 is cruicial for exerting killer activity of NK cells0

    • Author(s)
      Mika, Kijima, et. al.
    • Organizer
      The 37th Annual Meeting of the Japanese Society for Immunology
    • Place of Presentation
      Tokyo
    • Year and Date
      00001121
    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2010-02-04  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi