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Molecular Mechanism of Autoimmunity and its regulation

Research Project

Project/Area Number 09670495
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionNippon Medical School

Principal Investigator

NAKAJIMA Atsuo  Nippon Medical School Department of Rheumatology Assistant, 医学部, 助手 (10291725)

Co-Investigator(Kenkyū-buntansha) OKUMURA Ko  Juntendo University School of Medicine Department of Immunology Professor, 医学部, 教授 (50009700)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsSLE / RA / Th1 / Th2 / IL-4 / IL-12 / TNF / TNF family / chemokine / CCR5 / CCR4 / 関節リウマチ / co-stimulatory分子 / ケモカイン受容体 / Fas / Fas ligand / Apoptosis
Research Abstract

1 Our previous study demonstrated that both Thi and Th2 cytokines are involved in the development of lupus. In this study, to elucidate the complexity of cytokine regulation in the pathogenesis of autoimmunity in lupus, we first examined the role of IL-4 and IL-12. which play decisive roles In the development of Th2 and Thi, respectively, in NZB/W (B/W) Fl mice. Administration of mAb against either IL-4 or IL-12 before the onset of lupus could Inhibit the production of lgG anti-dsDNAAb. However, only anti-IL-4 mAb was effective In preventing the onset of lupus nephrltis. These results Indicate that both Th2 and Thi contribute to the lgG autoantibody production, and IL-4 is more critical. To further extend our understandings of Th2 development, we found that CDS6 costimulation plays a dominant role not only in the primary activation of Th2 cells but also in the secondary interaction between antigen primed Th2 cells and B cells. Next, we examined the contribution of B cell costimulatory … More molecules such as CD19 and CD21 to the development of lupus, we found that blockade of both CD19 and CD21 exacerbated murine lupus. These results Indicated that CD19 and CD21 were negatively regulated the onset of lupus.
2 To clarify the contribution of other costimulatory pathway, we focused on TNF/TNFreceptor family. Initially, we found that Fas/FasL interaction is involved in the destruction of hair follicles which is a characteristic feature of cutaneous lupus. Next, we found that inappropriate expression of CD4OL elicited anti-self immune response.
OX4OL-0X40 Interaction and CD7O-CD27 interaction were involved in the development of cell-mediated autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. 3 Recent studies have indicated that some chemokine receptors are differentially expressed on T helper (Th) 1 and Th2 cells, our results indicated that differential expression of chemokine receptors plays a critical role for selective recruitment of pro-inflammatory T cells Into the joints of RA. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Nakajuma, at al.: "Role of IL-4 and IL-12 in the development of lupus in NZB/W F1 mice." J.Immunol.Vol.158. 1466-1472 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakajima, et al.: "Requirement of CD28-CD86 co-stimulation in the interaction between antigen-primed T helper type 2 and B cells." Int.Immunol.Vol.9. 637-644 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakajima, et al.: "Expression of Fas ligand and its receptor in cutaneous lupus." Clin.Immunol. Immunopathol.Vol.83. 223-229 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakajima, et al.: "Inappropriate expression of CD40 ligand can elicit anti-selfimmune response." Arthritis Rheum.Vol.40. 132 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakajima, et al.: "Anti-Tumor Effect of CD40 Ligand : Elicitation of local and systemic anti-tumor responses by IL-12 and B7." J.Immunol.Vol.161. 1911-1918 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakajima, et al.: "Critical role of OX40/OX40L interaction in the development of autoimmune arthritis." Arthritis Rheum.Vol.41. 214 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Atsuo Nakajima, et al.: "Role of IL-4 and IL-12 in the development of lupus in NZB/W F1 mice." J.Immunol.158. 1466-1472 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Atsuo Nakajima, et al.: "Requirement of CD28-CD86 co-stimulation in the interaction between antigen-primed T helper type 2 and B cells." Int. Immunol.9. 637-644 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Toshiyasu Kawahara, et al.: "Involvement of Fas and Fas ligandinteraction in allogeneic hepatocyte rejection in spleen." Transplantation. Proc.29. 2187.1997 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Michiko Nakajima, Atsuo Nakajima, et al.: "Expression of Fas ligand and its receptor in cutaneous lupus." Clin.Immunol. Immunopathol.83. 223-229 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Toshiyasu Kawahara, et al.: "Critical role of Fas/Fas ligand interaction in CD28-independent pathway of allogenic hepatocyte rejection." Hepatology.26. 944 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Atsuo Nakajima, et al.: "Inappropriate expression of CD40 ligand can elicit anti-self immune response." Arthritis Rheum.Vol.40. 132 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shinji Morimoto, Tetsuji Kobata, Atsuo Nakajima, et al.: "Hyerexpression of CD27 and CD70 in patients with systemic lupus erythematosus and its role in pathogenic autoantibody production." Arthritis Rheum.Vol.40. 307 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Michiko Nakajima, Atsuo Nakajima, et al.: "Role of CD70/CD27 costimulatory pathway in the development of Th1-mediated autoimmunity." Arthritis Rheum.Vol.40. 225 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hideo Oshima, Hiroyasu Nakano, Chiyoko Nohara, Tetsiji Kobata, Atsuo Nakajima, et al.: "Characterization of murine CD70 by molecular cloning and mAb." Int.Immunol.10. 517-526 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Atsuo Nakajima, et al.: "Anti-Tumor Effect of CD40 Ligand : Elicitation of local and systemic anti-tumor responses by IL-12 and B7." J.Immunol.161. 1911-1918 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] R.Matsumura, K.Umeyama, M.Kagami, H.Tomioka, E.Tanabe, T.Sugiyama, A.Nakajima, et al.: "Glandular and extraglandular expression of the Fas-Fas ligand and apoptosis in patients with sjogren's syndrome." Clin.Exp.Rheumatol.16. 561-568 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nobuyuki Suzuki, Atsuo Nakajima, et al.: "Selective accumulation of CCR5^+ T lymphocytes into inflamed joint of rheumatoid arthritis." Int.Immunol.Vol.11.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Atsuo Nakajima, et al.: "Gritical role of OX40/OX40L interaction in the development of autoimmune arthritis." Arthritis Rheum.Vol.41. 214 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shinji Morimoto, Atsuo Nakajima, et al.: "The effect of anti-OX40 ligand antibody on the development of murine lupus." Arthritis Rheum.Vol.41. 174 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakajima et al.: "Role of CD70/CD27 costimulatory pathway in the development of Th1-mediated autoimmunity" Arthritis Rheum.Vol.40.225 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Oshima et al.: "Characterization of murine CD70 by molecular cloning and mAb." Int.Immunol.Vol.10. 517 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakajima et al.: "Anti-Tumor Effect of CD40 Ligand : Elicitation of local and systemic anti-tumor responses by IL-12 and B7" J.Immunol.Vol.161. 1911 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsumura et al.: "Glandular and extraglandular expression of the Fas-Fas ligand and apoptosis in patients with sjogren's syndrome" Clin.Exp.Rheumatol.Vol.16. 561 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Suzuki et al.: "Selective accumulation of CCR5^+T lymphocytes into inflamed joint of rheumatoid arthritis" Int.Immunol.Vol.11 in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakajima et al.: "Critical role of OX40/OX40L interaction in the development of autoimmune arthritis" Arthritis Rheum.Vol.41. 214 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakajima,A.et al.: "Roles of IL-4 and IL-12 in the development of lupus in NZB/W Fimice." Journal of lmmunology. 158. 1466-1472 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakajima,A.et al.: "Requirement of CD28-CD86 costimulation in the inferaction between anhgou-primed T helper type 2 and B cells." International lmmunology. 9. 637-644 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kawahara,T.et al.: "Invdvemeat of Fas and Fas ligand iuferaction in allogenic hepatoupte rejection in spleeu." Trausplautation Proceedings. 29. 2187-2188 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakajima et al.: "Expression of Fas ligand and its receptor in cutanecus lupus." Clinical lmmavology Immuropathdogy. 83. 223-229 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kawahara,T et al.: "Critical role of Fas/Fas ligand interaction in CD28-independent pathway of allogenic hepatocyte rejection" Hepatology. 26. 944-950 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakajima,A et al.: "lnappropriate expression of CD40 ligand can elicit auti-self immure respouse" Authritis and Rheumafisu. 40. 132 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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