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Analysis of the onset mechanisms of Psoriasis Vulgaris using transgenic mice

Research Project

Project/Area Number 10470188
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionOsaka University

Principal Investigator

YOSHIKAWA Kunihiko  Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (20110851)

Co-Investigator(Kenkyū-buntansha) KOSAKA Hiroshi  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (10260225)
SANO Shigetoshi  Osaka University Graduate School of Medicien Lecturer, 医学系研究科, 講師 (80273621)
ITAMI Satoshi  Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (30136791)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2000: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1999: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥5,900,000 (Direct Cost: ¥5,900,000)
KeywordsPsoriasis / Transgenic mice / Cross-Priming / CD8^+ T cells / stat3 / Ovalbumin / Antigen presentation / Homing / CD8^+T細胞 / CD4^+T細胞 / トランスジェニックマウス / 尋常性乾癬 / 表皮角化細胞 / T細胞 / 自己抗原 / 組織特異的
Research Abstract

Psoriasis is an inflammatory and proliferative disease of the skin. Some evidences indicate that psoriasis is a T-cell mediating autoimmune disease although the pathogenesis is still unclear. To study the onset mechanisms of psoriasis, here we have established transgenic mice.
Various cytokines may orchestrate the pathogenesis by controlling the interaction between T cells and keratinoctes. Among them, cytokines of IL6 family activate stat3 pathway. We have provided stat 3 conditional knock out mice (K5-Cre : Stat3^<flox/->) that loose stat 3 in keratinocytes by way of the cre-loxP strategy. These mutant mice have expressed spontaneous ulcers. This phenotype was not due to supressed proliferation but to impaired migration of keratinocytes.
Antigens expressed in keratinocytes are presumably targets for the autoimmune response of T cells. Based on this idea, we have established transgenic mice expressing chicken ovalbumin (OVA) as a model antigen under keratin-5 promoter (K5-mOVA). MHC class II promoter-mOVA transgenic (II-mOVA) mice were used as a control. From the experiment with transfer of OVA specific T cells (OT-I) into K5-mOVA, antigens expressed in the epidermis are constitutively presented to T cells in the draining lymph nodes. T cells recognized the antigen, followed by proliferation tha was detected with the CFSE method. T cells carryng green fluorescence protein (GFP) started infiltrating the skin on day 5 after transfer. This migration induced non-specific infiltration of host T cells and acanthosis as well. Some of OVA-specific TCR and K5-mOVA double transgenic mice showed inflammation of the skin and scaling although the incidence was around 5 percent. Now we are providing athymic (nude) K5-mOVA mice having been transplanted with TCR transgenic bone marrow, followed by transplantation with normal irradiated thymus to see whether T cells currently generated from the thymus induce skin diseas or not.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Sano,Shigetoshi et al: "Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling but does not affect skin morphogenesis"EMBO Journal. 18・17. 4657-68 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Allison,Jannette et al: "Transgenic overexpression of human Bcl-2 in islet beta cells inhibits apoptosis but does not prevent autoimmune destruction."International Immunology. 12・1. 9-17 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sano, Shigetoshi et al: "Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis"EMBO Journal. vol.18-17. 4657-68 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Allison, Jannette et al: "Transgenic overexpression of human Bcl-2 in islet beta cells inhibits apoptosis but does not prevent autoimmune destruction."International Immunology. vol.12-1. 9-17 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sano,Shigetoshi et al: "Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis"EMBO Journal. 18・17. 4657-68 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Allison,Jannette et al: "Transgenic overexpression of human Bcl-2 in islet beta cells inhibits apoptosis but does not prevent autoimmune destruction."International Immunology. 12・1. 9-17 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sano, Shigetoshi: "Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis"EMBO Journal. 18・17. 4657-4668 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.トクイ免疫反応:

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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