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Evaluation of immune suppressive therapy using autoimmune model mouse

Research Project

Project/Area Number 12557072
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Dermatology
Research InstitutionKeio University

Principal Investigator

NISHIKAWA Takeji  Keio University School of Medicine, Professor, 医学部, 教授 (50051579)

Co-Investigator(Kenkyū-buntansha) KOYASU Shigeo  Keio University School of Medicine, Professor, 医学部, 教授 (90153684)
ISHIKO Akira  Keio University School of Medicine, Assistant Professor, 医学部, 専任講師 (10202988)
AMAGAI Masayuki  Keio University School of Medicine, Assistant Professor, 医学部, 専任講師 (90212563)
鈴木 春己  慶応義塾大学, 医学部, 専任講師 (70235985)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2001: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2000: ¥7,800,000 (Direct Cost: ¥7,800,000)
KeywordsAutoimmune / Autoantibody / Model mouse / Pemphigus / desmoglein / Immune suppression / Therapy / cadherin / 天庖瘡
Research Abstract

Treatment regime for rare diseases, such as autoimmune diseases, are mostly based on personal experiences and each treatment lacks objective evaluation. This is largely due to the lack of animal models which well mimic the corresponding human diseases. We have recently developed a novel active disease mouse model using autoantigen knockout mouse, which does not require immune tolerance against the defective autoantigen. The purpose of this study is to develop an evaluation system of various immune suppressive therapeutic strategies using the autoimmune disease mouse model. Dsg3 -/- mice, which originally had a mixed genetic background of 129 and C57BL/6 mouse, were backcrossed to C57BL/6 and Balb/C mouse by 10 generation to reduce the difference of immune response of each individual mouse. A large mouse colony was established to supply a sufficient number of model mice for this assay. An objective score to evaluate the disease activity of the model mouse considering number of skin lesions, weight loss and patchy hair loss. The usefulness of our system was confirmed by evaluating a novel therapeutic strategy using anti-CD40L monoclonal antibody. In the future various therapeutic strategies will be evaluated with our system using the model mouse

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Amagai M, Tsunoda K, Suzuki H, Nishifuji K, Koyasu S, Nishikawa T: "Use of autoantigen knockout mice to develop an active autoimmune disease model of pemphigus"J Clin Invest. 105. 625-631 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Futei Y, Amagai M, Sekiguchi M, Nishifuji K, Fujii Y, Nishikawa T: "Conformational eptiope mapping of desmoglein 3 using domain-swapped molecules in pemphigus vulgaris"J Invest Dermatol. 115. 829-834 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sekiguchi M, Futei Y, Fujii Y, Iwasaki T, Nishikawa T, Amagai M: "Dominant autoimmune epitopes recognized by pemphigus antibodies map to the N-terminal adhesive region of desmogleins"J Immunol. 167. 5439-5448 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsunoda K, Ota T, Suzuki H, Ohyama M, Nagai T, Nishikawa T, Amagai M: "Pathogenic autoantibody production requires loss of tolerance against desmoglein 3 in both T and B cells in experimental"Eur J Immunol. 32. 627-633 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Cheng SW, Kobayashi M, Tanikawa A, Kinoshita-Kuroda K, Amagai M: "Monitoring disease activity in pemphigus with enzyme-linked immunosorbent assay using recombinant desmoglein 1 and 3"Br J Dermatol. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohyama M, Amagai M, Tsunoda K, Ota T, Koyasu S, Umezawa A, Hata J: "Immunologic and histopathologic characterization of active disease mouse model for pemphigus vulgaris"J Invest Dermatol. 118. 199-204 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Amagai M, Tsunoda K, Suzuki H, Nishifuji K, Koyasu S, Nishikawa T: "Use of autoantigen knockout mice to develop an active autoimmune disease model of pemphigus"J Clin Invest. 105. 625-631 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Futei Y, Amagai M, Sekiguchi M, Nishifuji K, Fujii Y, Nishikawa T: "Conformational eptiope mapping of desmoglein 3 using domain-swapped molecules in pemphigus vulgaris"J Invest Dermatol. 115. 829-834 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sekiguchi M, Futei Y, Fujii Y, Iwasaki T, Nishikawa T, Amagai M: "Dominant autoimmune epitopes recognized by pemphigus antibodies map to the N-terminal adhesive region of desmogleins"J Immunol. 167. 5439-5448 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsunoda K, Ota T, Swzuki H, Ohyama M, Nagai T, Nishikawa T, Amagai M, Koyasu S: "Pathogenic autoantibody production requires loss of tolerance against desmoglein 3 in both T and B cells in experimental pemphigus vulgaris"Eur J Immunol. 32. 627-633 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohyama M, Amagai M, Tsunoda K, Ota T, Koyasu S, Umezawa A, Hata J, Nishikawa T: "Immunologic and histopathologic characterization of active disease mouse model for pemphigus vulgaris"J Invest Dermatol. 118. 199-204 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Cheng SW, Kobayashi M, Tanikawa A, KinoshitaKuroda K, Amagai M, Nishikawa T: "Monitoring disease activity in pemphigus with enzyme-linked immunosorbent assay using recombinant desmoglein 1 and 3"Br J Dermatol. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] sekiguchi M, Futei Y, Fujil Y, Iwasaki T, Nishikawa T, Amagai M: "Dominant autoimmune epitopes recognized by pemphigus antibodies map to the N-terminal adhesive region of desmogleins"J Immunol. 167. 5439-5448 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsunoda K, Ota T, Suzuki H, Ohyama M, Nagai T, Nishikawa T, Amagai M, Koyasu S: "Pathogenic autoantibody production requires loss of tolerance against desmoglein 3 in both T and B cells in experimental pemphigus vulgaris"Eur J Immunol. 32. 627-633 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Cheng SW, Kobayashi A, Tanikawa A, Kinoshita-Kuroda K, Amagai M, Nishikawa T: "Monitoring disease activity in pemphigus with enzyme-linked immunosorbent assay using recombinant desmoglein 1 and 3"Br J Dermatol. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohyama M, Amagai M, Tsunoda K, Ota T, Koyasu S, Umezawa A, Hata J, NishikawaT: "Immunologic and histopathologic characterization of active disease mouse model for pemphigus vulgaris"J Invest Dermatol. 118. 199-204 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Futei Y, Amagai M, Ishii K, Kuroda-Kinoshita K, Ohya K, Nishikawa T: "Predominant IgG4 subclass in autoantibodies of pemphigus vulgaris and foliaceus"J Dermatol Sci. 26. 55-61 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Amagai M,Tsunoda K,Suzuki H,Nishifuji K,Koyasu S,Nishikawa T: "Use of autoantigen knockout mice to develop an active autoimmune disease model of pemphigus."J Clin Invest. 105. 625-631 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Futei Y,Amagai M,Sekiguchi M,Nishifuji K,Fujii Y,Nishikawa T: "Conformational eptiope mapping of desmoglein 3 using domain-swapped molecules in pemphigus vulgaris."J Invest Dermatol. 115. 829-834 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Proby CM,Ohta T,Suzuki H,Koyasu S,Gamou S,Shimizu N,Wheelock MJ,Nishikawa T,Amagai M: "Development of chimeric molecules for recognition and targeting of antigen-specific B cells in pemphigus vulgaris."Br J Dermatol. 142. 321-330 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nishifuji K,Amagai M,Kuwana M,Iwasaki T,Nishikawa T: "Detection of antigen-specific B cells in patients with pemphigus vulgaris by enzyme-linked immunospot (ELISPOT) Assay : requirement of T cell collaboration for autoantibody production."J Invest Dermatol. 114. 88-94 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hakuno M,Shimizu H,Akiyama M,Amagai M,Wahl JK,Wheelock MJ,Nishikawa T: "Dissociation of intra-and extracellular domains of desmosomal cadherins and E-cadherin in Hailey-Hailey disease and Darier's disease."Br J Dermatol. 143. 702-711 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Futei Y,Amagai M,Ishii K,Kinoshita K,Ohya K,Nishikawa T: "Predominant IgG4 subclass in autoantibodies of pemphigus vulgaris and foliaceus."J Dermatol Sci. (in press). (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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