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Molecular mechanisms of cell migration during T-lymphocyte development

Research Project

Project/Area Number 15390161
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

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)

Co-Investigator(Kenkyū-buntansha) UENO Tomoo  RIKEN, Research Center for Allergy and Immunology, Investigator, 免疫系発生研究チーム, 研究員 (30360506)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 2005: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2004: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2003: ¥4,800,000 (Direct Cost: ¥4,800,000)
KeywordsT lymphocyte / T cell-receptor / thymus / chemokine / CCR7 / positive selection / self-tolerance / cell migration / CCL19 / タイムラプス解析
Research Abstract

This study was aimed to identify the molecules that govern cellular migration during T-lymphocyte development in the thymus. Our results showed that (1)two chemokines CCL21 and CCL25, which are secreted by thymic epithelial cells, play a major role in attracting T-lymphoid progenitor cells to fetal thymus. We also showed that (2)chemokine signals via CCL19/CCL21 and CCR7 essentially regulate the migration of positively selected thymocytes from the thymic cortex to the thymic medulla. It was identified that the chemokine-dependent cortex-to-medulla migration of developing thymocytes was essential for establishment of central tolerance to tissue-specific antigens and not for T-cell maturation or T-cell export from adult thymus. Furthermore, our study showed that the emigration of mature T lymphocytes from the thymus was dependent on CCR7 chemokine signals in newborn mice but not in adult mice. These results have contributed to better understanding of molecular mechanisms that govern cellular migration during T-lymphocyte development in the thymus.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (50 results)

All 2006 2005 2004 Other

All Journal Article (38 results) Book (5 results) Publications (7 results)

  • [Journal Article] IAN family critically regulates survival and development of T lymphocytes.2006

    • Author(s)
      Nitta T, et al.
    • Journal Title

      PLoS Biology 4

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] CCR7-dependent cortex-medulla migration of positively selected thymocytes is essential for establishing central tolerance.2006

    • Author(s)
      Kurobe H, et al.
    • Journal Title

      Immunity 24

      Pages: 165-177

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Journey through the thymus : stromal guides for T-cell development and selection.2006

    • Author(s)
      Takahama Y.
    • Journal Title

      Nature Reviews Immunology 6

      Pages: 127-135

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Cellular and molecular events during early thymus development.2006

    • Author(s)
      Hollander G, et al.
    • Journal Title

      Immunological Reviews 209

      Pages: 28-46

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Development of autoimmunity against transcriptionally unrepressed target antigen in the thymus from Aire-deficient mice2006

    • Author(s)
      Kuroda N, et al.
    • Journal Title

      J Immunol. 174

      Pages: 1862-1870

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Thymic involution produced by diesel exhaust particles and their constituents in mice.2006

    • Author(s)
      Tomita S
    • Journal Title

      Toxicology and Environmental Chemistry (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] IAN family critically regulates survival and development of T lymphocytes.2006

    • Author(s)
      Nitta T, Nasreen M
    • Journal Title

      PLoS Biology. 4(4):e103

      Pages: 1-13

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CCR7-dependent cortex-to-medulla migration of positively selected thymocytes is essential for establishing central tolerance.2006

    • Author(s)
      Kurobe H
    • Journal Title

      Immunity. 24

      Pages: 165-177

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Journey through the thymus : stromal guides for T-cell development and selection.2006

    • Author(s)
      Takahama Y.
    • Journal Title

      Nature Rev Immunol. 6

      Pages: 127-135

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cellular and molecular events during early thymus development.2006

    • Author(s)
      Hollander G
    • Journal Title

      Immunol.Rev. 209

      Pages: 28-46

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CCR7-dependent cortex-medullamigration of positively selected thymocytes is essential for establishing central tolerance.2006

    • Author(s)
      Kurobe H, et al.
    • Journal Title

      Immunity 24

      Pages: 165-177

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Controlling the thymic microenvironment.2005

    • Author(s)
      Gray D, et al.
    • Journal Title

      Current Opinion in Immunology 17

      Pages: 137-143

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] The role of CCL21 in recruitment of T-precursor cells to fetal thymi.2005

    • Author(s)
      Liu C, et al.
    • Journal Title

      Blood 105

      Pages: 31-39

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Controlling the thymic microenvironment.2005

    • Author(s)
      Gray DHD
    • Journal Title

      Curr Op Immunol. 17

      Pages: 137-143

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Development of autoimmunity against transcriptionally unrepressed target antigen in the thymus from Aire-deficient mice.2005

    • Author(s)
      Kuroda N
    • Journal Title

      J Immunol. 174

      Pages: 1862-1870

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The role of CCL21 in recruitment of T-precursor cells to fetal thymi.2005

    • Author(s)
      Liu C
    • Journal Title

      Blood. 105

      Pages: 31-39

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The role of CCL21 in recruitment of T precursor cells to fetal thymus.2005

    • Author(s)
      Liu C, et al.
    • Journal Title

      Blood 105

      Pages: 31-39

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The role of CCL21 in recruitment of T precursor cells to fetal thymus.2005

    • Author(s)
      Liu C, et al.
    • Journal Title

      Blood. 105

      Pages: 31-39

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Increased frequency of aberrant V(D)J recombination products in core RAG-expressing mice.2004

    • Author(s)
      Talukder SR, et al.
    • Journal Title

      Nucleic Acids Res 32

      Pages: 4539-4549

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CCR7 signals are essential for cortex-to medulla migration of developing thymocytes.2004

    • Author(s)
      Ueno T, et al.
    • Journal Title

      The Journal of Experimental Medicine 200

      Pages: 493-505

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mutations affecting thymus organogenesis in medaka, Oryzias latipes2004

    • Author(s)
      Iwanami N, et al.
    • Journal Title

      Mech Dev. 121

      Pages: 779-789

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A systematic genome-wide screen for mutations affecting organogenesis in Medaka, Oryzias latipes.2004

    • Author(s)
      Furutani-Seiki M, et al.
    • Journal Title

      Mech Dev. 121

      Pages: 647-658

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Mutations affecting liver development and function in Medaka, Oryzias latipes.2004

    • Author(s)
      Watanabe T, et al.
    • Journal Title

      Mech Dev. 121

      Pages: 791-801

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mutations affecting somite formation in the Medaka (Oryzias latipes).2004

    • Author(s)
      Elmasri H, et al.
    • Journal Title

      Mech Dev. 121

      Pages: 659-671

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] NF-kB-inducing kinase establishes self-tolerance in a thymic-stroma dependent manner.2004

    • Author(s)
      Kajiura F, et al.
    • Journal Title

      J Immunol. 172

      Pages: 2067-2075

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Developmental status of CD4-CD8+ and CD4+CD8- thymocytes with medium expression of CD3.2004

    • Author(s)
      Sheard MA, et al.
    • Journal Title

      Eur J Immunol. 34

      Pages: 25-35

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Increased frequency of aberrant V(D)J recombination products in core RAG-expressing mice.2004

    • Author(s)
      Talukder SR
    • Journal Title

      Nucleic Acids Res. 32

      Pages: 4539-4549

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CCR7 signals are essential for cortex-to-medulla migration of developing thymocytes.2004

    • Author(s)
      Ueno T
    • Journal Title

      J Exp Med. 200

      Pages: 493-505

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mutations affecting thymus organogenesis in medaka, Oryzias latipes.2004

    • Author(s)
      Iwanami N
    • Journal Title

      Mech Dev. 121

      Pages: 779-789

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A systematic genome-wide screen for mutations affecting organogenesis in Medaka, Oryzias latipes.2004

    • Author(s)
      Furutani-Seiki M
    • Journal Title

      Mech Dev. 121

      Pages: 647-658

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mutations affecting liver development and function in Medaka, Oryzias latipes.2004

    • Author(s)
      Watanabe T
    • Journal Title

      Mech Dev. 121

      Pages: 791-802

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mutations affecting somite formation in the Medaka (Oryzias latipes).2004

    • Author(s)
      Elmasri H
    • Journal Title

      Mech Dev. 121

      Pages: 659-671

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] NF-kB-inducing kinase establishes self-tolerance in a thymic-stroma dependent manner.2004

    • Author(s)
      Kajiura F
    • Journal Title

      J Immunol. 172

      Pages: 2067-2075

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Developmental status of CD4-CD8+ and CD4+CD8- thymocytes with medium expression of CD3.2004

    • Author(s)
      Sheard MA
    • Journal Title

      Eur J Immunol. 34

      Pages: 25-35

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Increased frequency of aberrant V(D)J recombination products in core RAG-expressing mice.2004

    • Author(s)
      Talukder SR, et al.
    • Journal Title

      Nucleic Acids Res. 32

      Pages: 4539-4549

    • Related Report
      2004 Annual Research Report
  • [Journal Article] CCR7 signals are essential for cortex-to-medulla migration of developing thymocytes.2004

    • Author(s)
      Ueno T, et al.
    • Journal Title

      J Exp Med. 200

      Pages: 493-505

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mutations affecting thymus organogenesis in medaka, Oryzias latipes.2004

    • Author(s)
      Iwanami N, et al.
    • Journal Title

      Mech Dev. 121

      Pages: 779-789

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Thymic involution produced by diesel exhaust particles and their constituents in mice.

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

      Toxicology and Environmental Chemistry (In Press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Current Protocols in Immunology.2006

    • Author(s)
      Ramsdell F, et al.
    • Publisher
      John Wiley & Sons, NJ, USA(In Press)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] In vitro systems for the study of T cell development : fetal thymus organ culture and OP9-DL1 cell coculture(Current Protocols in Immunology.)2006

    • Author(s)
      Ramsdell F
    • Publisher
      John Wiley & Sons, NJ, USA(in press)
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Basic Cell Culture Protocols, Third Edition2005

    • Author(s)
      Ueno T, et al.
    • Total Pages
      17
    • Publisher
      Humana Press, NJ, USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Book] The development of T lymphocytes in mosue fetal thymus organ culture.(Basic Cell Culture Protocols)2005

    • Author(s)
      Ueno T
    • Publisher
      Humana Press, NJ, USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Basic Cell Culture Protocols2004

    • Author(s)
      Ueno T, et al.
    • Total Pages
      17
    • Publisher
      Humana Press, NJ, USA
    • Related Report
      2004 Annual Research Report
  • [Publications] Sheard, M.A., et al.: "Development status of CD4-CD8+ and CD4+CD8- thymocytes with medium expression of CD3"Eur.J.Immunol.. 34. 25-35 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nasreen, M., et al.: "In vivo treatment of class II MHC-deficient mice with anti-TCR antibody restores the generation of circulating CD4 T cells and optimal architecture of thymic medulla"J.Immunol.. 171. 3394-3400 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tomita, S., et al.: "Defective brain development in mice lacking the HIf-1alpha gene in neural cells"Mol.Cell.Biol.. 23. 6739-6749 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tomita, S., et al.: "T cell-specific disruption of aryl hydrocarbon receptor nuclear translocator (Arnt) gene causes resistance to 2378-tetrachlorodibenzo-p-dioxin-induced thymic involution"J.Immunol. 171. 4113-4120 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akamatsu, Y., et al.: "Deletion of the RAG2 C-terminus leads to impaired lymphoid development in mice"Proc.Natl.Acad.Sci.USA.. 100. 1209-1214 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakase H., et al.: "Effect of CpG methylation on RAG1/RAG2 reactivity : implications of direct and indirect mechanisms for controlling V(D)J cleavage"EMBO Reports. 4. 774-780 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ueno, T., et al.: "In Basic Cell Culture Protocols"Humana Press, NJ, USA(In press). (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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