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Research for the prevention of tumor cell metastasis based on the establishment of artificial lymph node genesis

Research Project

Project/Area Number 14570278
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionRIKEN (The Institute of Physical and Chemical Research)

Principal Investigator

YOSHIDA Hisahiro  RIKEN (The Institute of Physical and Chemical Research), Immune System Development Group, Senior scientist, 免疫系構築グループ, 上級研究員 (20281090)

Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsPeripheral lymph nodes / chemokine / CXCL13 / IL7Ra+ cells / LT・・ / VCAM-1 / ICAM-1+ mesenchymal cells / TRAF6 / Long term culture / 末梢リンパ器官 / IL-7R陽性細胞 / ICAM-1二重陽性細 / リンフォトキシン / 末梢リンパ器官再生 / IL7R / 間質細胞 / LTab
Research Abstract

We have found that murine peripheral lymph nodes (PLN) anlagen develop in multi steps listed below,
1.Local expression of chemokine CXCL13 at PLN anlagen,
2.Migration of IL-7Ra+ cells to those anlagen,
3.Stimulation of IL-7Ra+ cells by local specific cytokines and expression of lymphotoxin (LT) ab by IL-7Ra+ cells,
4.Differentiation of specific mesenchyme cells by LTab and expression of adhesion molecules and chemokines by mesenchymal cells,
5.Migration of various lineage leukocytes to PLN anlagen,
6.Development of micro-architecture of PLN anlagen, including endothelial cells development.
In accordance with these developmental scheme, we tried to culture the key player of PLN development, IL-7Ra+ cells (inducer cells), and VCAM-1+ICAM-1+ mesenchymal cells (organizer cells). Although we have succeeded to culture the former more than 10 weeks in in vitro condition, we failed to culture the latter cells longer than 2 weeks. Then we transferred those in vitro cultivated cells to the nude mouse subcutaneous region. However, the transferred cells did not induced artificial PLN tissue. As we have found that CXCL13 is a key molecule to keep the inducer cells to PLN anlagen, we are still trying to find out the best condition to keep them in in vivo with multiple molecules those participate in PLN organogenesis

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Yoshida, H.: "Different cytokines are inducers of surface lymphotoxin-alpha/beta on IL-7 receptor-alpha cells that differentially engender lymph nodes and Peyer's patches"Immunity. 17. 823-833 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishimura, E.K.: "Dominant role of the niche in melanocyte stem-cell fate determination"Nature. 416. 854-860 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Naito, A.: "TRAF6-deficient mice display hypohidrotic ectodermal dysplasia"Proc Natl Acad Sci USA. 99. 8766-8771 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukuda, K.: "Mesenchymal expression of Fox11, a winged helix transcriptional factor, regulates generation and maintenance of gut associated lymphoid organs"Developmental Biology. 255. 278-289 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iiyama, R.: "Normal development of the gut-associated lymphoid tissue except Peyer's patch in MyD88-deficient mice"Scand J Immunol. 58. 620-627 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishikawa, S.-I.: "Organogenesis of peripheral lymphoid organs"Immunological Reviews. 195. 72-80 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshida, H.: "Different cytokines are inducers of surface lymphotoxin-alpha/beta on IL-7 receptor-alpha cells that differentially engender lymph nodes and Peyer's patches."Immunity. 17. 823-833 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishimura EK: "Dominant role of the niche in melanocyte stem-cell fate determination."Nature. 416. 854-860 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Naito A: "TRAF6-deficient mice display hypohidrotic ectodermal dysplasia."Proc Natl Acad Sci U S A. 99. 8766-8771 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukuda, K.: "Mesenchymal expression of Foxl1,a winged helix transcriptional factor, regulates generation and maintenance of gut associated lymphoid organs."Developmental Biology. 255. 278-289 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iiyama, R.: "Normal development of the gut-associated lymphoid tissue except Peyer's patch in MyD88-deficient mice."Scand J Immunol. 58. 620-627 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishikawa, S.-I.: "Organogenesis of peripheral lymphoid organs"Immunological Reviews. 195. 72-80 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishikawa, S.-I., et al.: "Organogenesis of peripheral lymphoid organs"Immunological Reviews. 195. 72-80 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iiyama, R., et al.: "Normal development of the gut associated lymphoid tissue except Peyer's patch in MyD88-deficient mice."Scand J Immunol. 58. 620-627 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Weston JA, et al.: "Neural crest and the origin of ectomesenchyme : Neural fold heterogeneity suggests an alternative hypothesis."Dev Dyn.. 229. 118-130 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yuhki, M., et al.: "BMP receptor IA signaling is necessary for hair follicle cycling and hair shaft differentiation in mice."Development. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishimura EK, Jordan SA, Oshima H, Yoshida H, et al.: "Dominant role of the niche in melanocyte stem-cell fate determination"Nature. 416. 854-860 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Naito A, Yoshida H, Nishioka B, Satoh M, Azuma S, Yamamoto T, Nishikawa S, Inoue: "TRAF6-deficient mice display hypohidrotic ectodermal dysplasia"Proc Nati Acad Sci U S A.. 99. 8766-8771 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Murakami H, Okawa A, Yoshida H, Nishikawa S, Koseki H, et al.: "Elbow knee synostosis (Eks): a new mutation on mouse Chromosome 14."Mamm Genome.. 13. 341-344 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nishioka E, Tanaka T, Yoshida H, Matsuinura K, et al.: "Mucosal addressin cell adhesion molecule 1 plays an unexpected role in the development of mouse guard hair"J Invest Dermatol.. 119. 632-638 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshida, H., Naito, A., Inoue, JI., Satoh, M., Santee-Cooper, et al.: "Different cytokines are inducers of surface lymphotoxin-alpha/beta on IL-7 receptor-alpha cells that differentially engender lymph nodes and Peyer's patches"Immunity. 17. 823-833 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fukuda, K., Yoshida., H., Sato, T., Furumoto, T., et al.: "Mesenchymal expression of Foxll, a winged helix transcriptional factor, regulates aeneration and maintenance of gut associated lymphoid organs."Developmental Biology. (in press). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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