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2006 Fiscal Year Final Research Report Summary

Research of the roles of PD-1/PD-Ligand in human lupus nephritis and murine lupus-like nephritis

Research Project

Project/Area Number 17591042
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionKobe University

Principal Investigator

KAWANO Seiji  Kobe University Hospital, Lecturer, 医学部附属病院, 講師 (20351512)

Co-Investigator(Kenkyū-buntansha) KUMAGAI Shunich  Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (00153346)
MORINOBU Akio  Kobe University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10294216)
Project Period (FY) 2005 – 2006
KeywordsPD-1 / Periferal tolerance / Lupus nephritis / NZB / W
Research Abstract

Autoimmune diseases develop as a result of the breakage of tolerance in a combination of genetic backgrounds and various exogenous factors. In lupus nephritis, it is supposed that some unknown factors may trigger and lead to the breakage of peripheral tolerance, resulting in the activation and survival of self-reactive T cells that promote autoimmune process. Recently, B7-CD28 family molecules have revealed their crucial roles in activation and post-activation regulation of T cells. PD-1, one of B7 family receptor and transmitting immunosuppressive signals to lymphocytes, is supposed to be very important in the maintenance of peripheral tolerance, since the murine knockout models have been reported to cause autoimmune-disease-like symptoms. Interestingly, PD-L1 is distributed in epithelia of various peripheral tissues.
We analyzed whether there was abnormality of PD-1/PD-L system in a lupus nephritis model, NZB/W F1 mouse, and examined whether lupus-like nephritis develop when you modify the PD-1/PD-L system. We confirmed the expression of PD-1/PD-L1 in the kidney of NZB/W F1 mouse. PD-1 was expressed on infiltrating lymphocytes, and PD-L1 was on infiltrating lymphocytes, glomerular cells, and tubular cells. Next, we performed intraperitoneal injection of anti-PD-L1 antibody to NZB/W F1 mice for three months. Urine protein appeared in the anti-PD-L1 antibody-treated group earlier than in non-treated group, and about half of mice died early in anti-PD-L1 treated group. Therefore, we concluded that the anti-PD-L1 antibody treatment exacerbated nephritis. In addition, serum interferon γ level was markedly increased in antibody-treated group.
In conclusion, PD-1/PD-L system is closely related to the development of lupus-like nephrits, and we expect that future studies will help to develop a therapeutic method to cure lupus nephritis, or other autoimmune diseases.

  • Research Products

    (4 results)

All 2006 2005

All Journal Article (3 results) Book (1 results)

  • [Journal Article] 唾液腺におけるPD-1/PD-1発現 Page(2006.05)2006

    • Author(s)
      河野誠司
    • Journal Title

      臨床免疫 45巻・5号

      Pages: 571-577

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Enhanced expression of PD-1/PD-L1 in salivary gland of patients with Sjogren's syndrome.2005

    • Author(s)
      Kobayashi M
    • Journal Title

      J Rheumatol 32巻・11号

      Pages: 2156-2163

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Enhanced expression of PD-1/PD-L1 in salivary gland of patients with SjOgren's syndrome.2005

    • Author(s)
      Kobayashi M, Kawano S, Hatachi S, Kurimoto, Okazaki T, Iwai Y, Honjo T, Tanaka Y, Minato N, Komori T, Maeda S, Kumagai S.
    • Journal Title

      J Rheumatol 32(11)

      Pages: 2156-2163

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Oxidative stress and autoimmune diseases.Oxidative stress, disease and cancer.(In : Singh KK editor.)2006

    • Author(s)
      Saegusa J.
    • Total Pages
      16
    • Publisher
      London : Imperial college press.
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2008-05-27  

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