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Role of CCL19/ 21 chemokine in the development of experimental autoimmune encephalomyelitis

Research Project

Project/Area Number 17590900
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionToho University

Principal Investigator

KAKIUCHI Terutaka  Faculty of medicine, Professor, 医学部, 教授 (40126024)

Co-Investigator(Kenkyū-buntansha) IWASAKI Yasuo  Faculty of medicine, Professor, 医学部, 教授 (30130347)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsplt mouse / CCL21 chemokine / CCL19 chemokine / IL-17 / IL-23 / T cell / EAE / multiple sclerosis
Research Abstract

Experimental autoimmune encephalomyelitis (EAE) in mouse is a model of multiple sclerosis. We have investigated the role of CCL21/19 chemokine in the regulation of immune response, using mutant mouse lacking the expression of CCL19/21 (paucity of lymph node T cells: plt) which was found in our laboratory. During investigation, we found that these mutant mice are resistant to the induction of EAE. In the present study, we analyzed the mechanisms for the resistance, and obtained following results.
(1) Recently, it has been established that Th-17 cells other than Th-1 cells are responsible to the development of EAE. In plt mice Th-17 cells did not differentiated after immunization with myelin-oligodendrocyte glycoprotein (MOG) 35-55 peptide in CFA, which induced Th-17 cells and EAE in wild type (WT) mice.
(2) IL-6, TGF-beta and IL-23 are required for the production of IL-17. When draining lymph node cells were incubated, IL-6 and TGF-beta were detected in the culture supernatant of the lymph node cells from plt mice similarly to that from WT mice, IL-23 was very low.
(3) Addition of IL-23 to the culture of CD4+ T cells from draining lymph nodes of plt mice induced production of IL-17.
(4) The addition of CCL21 chemokine to the culture of CD4+ T cells from draining lymph nodes of plt mice was not effective to the induction of IL-17 production.
(5) Purified CD11c+ dendritic cells produced IL-23 in the presence of CCL21.
(6) CD11c+ dendritic cells from CCR7-deficient mice did not produce IL-23 even when CCL21 was present.
These results suggested that in plt mice Th-17 cells were not induced due to the lack of IL-23, which was resulted from the deficient stimulation of CCR7 in the mice lacking the expression of CCL21/19 chemokine.
Our next project is developing the procedures to treat EAE by manipulating IL-23 or CCL21/19 chemokine.

Report

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

    (15 results)

All 2007 2006 2005

All Journal Article (13 results) Book (2 results)

  • [Journal Article] Chemokines CCL19 and CCL21 promote activation-induced cell death of antigen-responding T cells.2007

    • Author(s)
      Yasuda T, Kuwabara T, Nakano H, Aritomi K, Onodera T, Lipp M, Takahama Y, Kakiuchi T.
    • Journal Title

      Blood 109・2

      Pages: 449-456

    • 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] Chemokines CCL19 and CCL21 promote activation-induced cell death of antigen-responding T cells.2007

    • Author(s)
      Yasuda T, Kuwabara T, Nakano H, Aritomi K, Onodera T, Lipp M, Takahama Y, Kakiuchi T.
    • Journal Title

      Blood 109-2

      Pages: 449-56

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Inhibition of MHC class II expression and immune responses by c-MIR.2006

    • Author(s)
      Ohmura-Hoshino M, Matsuki Y, Aoki M, Goto E, Mito M, Uematsu M, Kakiuchi T, Hotta H, Ishido S.
    • Journal Title

      J Immunol 177・1

      Pages: 341-354

    • 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] Role of CCL21 and CCL19 in allergic inflammation in the ovalbumin-specific murine asthmatic model.2006

    • Author(s)
      Yamashita N, Tashimo H, Matsuo Y, Ishida H, Yoshiura K, Sato K, Yamashita N, Kakiuchi T, Ohta K.
    • Journal Title

      J Allergy Clin Immunol 117・5

      Pages: 1040-1046

    • 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] Loss of dendritic cell migration and impaired resistance to Leishmania donovani infection in mice deficient in CCL19 and CCL21.2006

    • Author(s)
      Ato M, Maroof A, Zubairi S, Nakano H, Kakiuchi T, Kaye PM.
    • Journal Title

      J Immunol 176・9

      Pages: 5486-5493

    • 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] Inhibition of MHC class II expression and immune responses by c-MIR.2006

    • Author(s)
      Ohmura-Hoshino M, Matsuki Y, Aoki M, Goto E, Mito M, Uematsu M, Kakiuchi T, Hotta H, Ishido S.
    • Journal Title

      J Immunol 177-1

      Pages: 341-354

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Role of CCL21 and CCL19 in allergic inflammation in the ovalbumin-specific murine asthmatic model.2006

    • Author(s)
      Yamashita N, Tashimo H, Matsuo Y, Ishida H, Yoshiura K, Sato K, Yamashita N, Kakiuchi T, Ohta K.
    • Journal Title

      J Allergy Clin Immunol 117-5

      Pages: 1040-46

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Loss of dendritic cell migration and impaired resistance to Leishmania donovani infection in mice deficient in CCL19 and CCL21.2006

    • Author(s)
      Ato M, Maroof A, Zubairi S, Nakano H, Kakiuchi T, Kaye PM.
    • Journal Title

      J Immunol 176-9

      Pages: 5486-93

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] CXCL9 antagonism further extends prolonged cardiac allograft survival in CCL19/CCL21-deficient mice.2005

    • Author(s)
      Colvin BL, Wang Z, Nakano H, Wu W, Kakiuchi T, Fairchild RL, Thomson AW.
    • Journal Title

      Am J Transplant 5・9

      Pages: 2104-2113

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Negatively charged phospholipids suppress IFN-gamma production in T cells.2005

    • Author(s)
      Yotsumoto S, Kakiuchi T, Aramaki Y
    • Journal Title

      Biochem Biophys Res Commun 338・4

      Pages: 1719-1725

    • 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] CXCL9 antagonism further extends prolonged cardiac allograft survival in CCL19/CCL21-deficient mice.2005

    • Author(s)
      Colvin BL, Wang Z, Nakano H, Wu W, Kakiuchi T, Fairchild RL, Thomson AW.
    • Journal Title

      Am J Transplant 5-9

      Pages: 2104-13

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Negatively charged phospholipids suppress IFN-gamma production in T cells.2005

    • Author(s)
      Yotsumoto S, Kakiuchi T, Aramaki Y
    • Journal Title

      Biochem Biophys Res Commun 338-4

      Pages: 1719-25

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] CXCL9 antagonism further extends prolonged cardiac allograft survival in CCL19/CCL2l-deficient mice.2005

    • Author(s)
      Colvin BL, Wang Z, Nakano H, Wu W, Kakiuchi T, Fairchild RL, Thomson AW.
    • Journal Title

      Am J Transplant 5・9

      Pages: 2104-2113

    • Related Report
      2005 Annual Research Report
  • [Book] 免疫学ハンドブック2005

    • Author(s)
      垣内史堂 他
    • Total Pages
      521
    • Publisher
      オーム社
    • 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
  • [Book] Immunology handbook2005

    • Author(s)
      Kakiuchi T, et al.
    • Total Pages
      521
    • Publisher
      Ohmsha, Ltd
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary

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

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