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The roles of HIF-1α in T cell-dependent immune responses

Research Project

Project/Area Number 17590436
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

TOMITA Shuhei  The University of Tokushima, Institute for Genome Research, Associate Professor, ゲノム機能研究センター, 助教授 (00263898)

Co-Investigator(Kenkyū-buntansha) TAKAHAMA Yousuke  The University of Tokushima, Institute for Genome Research, Professor, ゲノム機能研究センター, 教授 (20183858)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsHypoxia / T cell / HIF-1 / immune responses / knock out
Research Abstract

A basic HLH-PAS transcription factor, hypoxia inducible factor-1α (HIF-1α) facilitates the adaptation of cells to oxygen deprivation, by regulating the genes that are involved in glucose uptake, angiogenesis, erythropoiesis, and cell survival. When T cells migrate from lymph node or the circulation to peripheral inflammation site for immune response, they should be required to adapt to and function within oxygen tensions much lower than those encountered in circulation system. To investigate the role of HIF-1α in peripheral T cells in vivo, we generated T cell-specific HIF-1α KO mice by crossing HIF-1α floxed mice with proximal lck promoter-driven Cre-transgenic mice. We found that HIF-1α-KO T cells were normally generated in the thymus and their distribution in the spleen, and lymph nodes was unimpaired. In the in. vitro culture conditions, HIF-1α-deficient T cells exhibited undiminished IL-2/IL-2R production and proliferation upon stimulation with either anti-CD3 antibody or Con A. I … More n this fiscal year, we have examined whether T cell-mediated responses in HIF-1α KO mice also show consistent results to in vitro experiment described above.
The inflammatory process mediated by monocytes/macrophages and T cells plays a role in atherosclerosis and vascular remodeling. HIF-1alpha has also been shown to be related to T cell functions; however, its role in inflammation and vascular remodeling still unknown clearly. To use this model would lead to us how HIF-1α in T cells contributes to immune response in vivo.
Cuff placement caused significant neointimal hyperplasia in HIF-1α KO mice compared with the control (intima/media< intima/lumen > ratio: 0.28 <0.31> in HIF-1α KO mice with cuff replacement vs. 0.07 <0.06> in those without cuff replacement). However, there was no obvious exacerbation of cuff-injured vascular remodeling in WT and ARNT KO mice. H&E staining showed that infiltration of mononuclear cells, including plasma cells, at the adventitia was remarkably increased in HIF-1α KO mice but increased only slightly in WT mice and ARNT KO mice.
The HIF-1 signaling pathway in T cells plays a crucial role in the progression of arteriosclerosis. Understanding the molecular mechanism of how HIF-1 signaling pathway is involved in atherosclerosis will provide a therapeutic target for the development of new drugs against atherosclerosis. Less

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (21 results)

All 2007 2006 2005

All Journal Article (21 results)

  • [Journal Article] p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload.2007

    • Author(s)
      Sano M
    • Journal Title

      Nature (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload.2007

    • Author(s)
      Sano M
    • Journal Title

      Nature (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] p53-induced inhibition of Hif-1 causes cardiac dysfunction durin gpressure overload.2007

    • Author(s)
      Sano M
    • Journal Title

      Nature (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Two pathways of apoptosis are simultaneously induced in the embryonal brains of neural cell-specific HIF-1alpha-deficient mice.2006

    • Author(s)
      Ueno, M
    • Journal Title

      Histochem. Cell Biol. 125・5

      Pages: 535-544

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of aging and HIF-1alpha deficiency on permeability of hippocampal vessels.2006

    • Author(s)
      Ueno, M.
    • Journal Title

      Microsc. Res. Tech. 69・1

      Pages: 29-35

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Diesel exhaust particles and their components that are independent of polycyclic aromatic hydrocarbons cause thymic involution in mice.2006

    • Author(s)
      Tomita, S.
    • Journal Title

      J. Toxico. Environ. Chem. 88

      Pages: 113-124

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] HIF1alpha-arnt transcriptional system of T lymphocytes may regulate the vascular inflammation and remodeling in the arteriosclerosis disease2006

    • Author(s)
      Kurobe H
    • Journal Title

      Atherosclerosis 7・3

      Pages: 235-235

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Disruption of the Arnt gene in endothelial cells causes hepatic vascular defects and partial embryonic lethality.2006

    • Author(s)
      Yim SH
    • Journal Title

      Hepatology 44・3

      Pages: 550-560

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Two pathways of apoptosis are simultaneously induced in the embryonal brains of neural cell-specific HIF-1alpha-deficient mice.2006

    • Author(s)
      Ueno, M
    • Journal Title

      Histochem.Cell Biol. 125・5

      Pages: 535-544

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of aging and HIF-1alpha deficiency on permeability of hippocampal vessels.2006

    • Author(s)
      Ueno, M.
    • Journal Title

      Microsc.Res.Tech. 69・1

      Pages: 29-35

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Diesel exhaust particles and their components that are independent of polycyclic aromatic hydrocarbons cause thymic involution in mice. J.2006

    • Author(s)
      Tomita, S.
    • Journal Title

      Toxico.Environ.Chem. 88

      Pages: 113-124

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] HIF1alpha-arnt transcriptional system of T lymphocytes may regulate the vascular inflammation and remodeling in the arteriosclerosis disease.2006

    • Author(s)
      Kurobe H
    • Journal Title

      Atherosclerosis 7・3

      Pages: 235-235

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of aging and HIF-1lapha deficiency on permeability of hippocampal vessels.2006

    • Author(s)
      Ueno, M.
    • Journal Title

      Microsc.Res.Tech. 69・1

      Pages: 29-35

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Diesel exhaust particles an dtheir components that are independent of polycyclic aromatic hydrocarbons cause thymic involution in mice.2006

    • Author(s)
      Tomita, S.
    • Journal Title

      J.Toxico.Environ.Chem. 88

      Pages: 113-124

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effects of again HIF-1alpha deficiency on permeability of hippocampal vessels.2006

    • Author(s)
      Ueno, M.
    • Journal Title

      Microsc. Res. Tech. 69・1

      Pages: 29-35

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Diesel exhaust particles and their components that are independent of polycyclic aromatic hydrocarbons cause thymic involution in mice.2006

    • Author(s)
      Tomita, S.
    • Journal Title

      J. Toxico. Environ. Chem. In press

    • Related Report
      2005 Annual Research Report
  • [Journal Article] ERK1/2 activation by angiotensin II inhibits insulin-induced glucose uptake in vascular smooth muscle cells.2005

    • Author(s)
      Izawa, Y
    • Journal Title

      Exp. Cell Res. 308・2

      Pages: 291-299

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] T cell-specific HIF-1alpha-deficient mice, but not ARNT-deficient mice, exhibit exacerbated inflammation and vascular remodeling in response to cuff injury2005

    • Author(s)
      Kurobe H
    • Journal Title

      Circulation 112・17

      Pages: 215-215

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] ERK1/2 activation by angiotensin II inhibits insulin-induced glucose uptake in vascular smooth muscle cells.2005

    • Author(s)
      Izawa, Y
    • Journal Title

      Exp.Cell Res. 308・2

      Pages: 291-299

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] T cell-specific HIF-1alpha-deficient mice, but not ARNT-deficient mice, exhibit exacerbated inflammation and vascular remodeling in response to cuff injury.2005

    • Author(s)
      Kurobe H
    • Journal Title

      Circulation 112・17

      Pages: 215-215

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Two pathways of apoptosis are simultaneously induced in the embryonal brains of neural cell-specific HIF-1alpha-deficient mice.2005

    • Author(s)
      Ueno, M
    • Journal Title

      Histochem. Cell Biol. e-pub ahead of print

      Pages: 1-10

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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