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2010 Fiscal Year Final Research Report

CD4 positive T cells directly associate with development of lupus nephritis.

Research Project

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Project/Area Number 21890204
Research Category

Grant-in-Aid for Research Activity Start-up

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

Principal Investigator

SEKINE Hideharu  Fukushima Medical University, 医学部, 講師 (40363759)

Research Collaborator GARY GILKESON  米国サウスカロライナ州立医科大学, 教授
Project Period (FY) 2008 – 2010
Keywords全身性エリテマトーデス / ループス腎炎 / インターフェロン調節因子4 / CD4陽性T細胞 / Th1 / Th17
Research Abstract

Lupus-prone MRL/lpr mice, that lack interferon regulatory factor 4 (Irf4-/-MRL/lpr), develop cellular proliferative glomerulonephritis with significantly increased numbers of splenic CD4+ T cells, despite lack of antibody production and immune complex (IC) formation. To investigate the underlying mechanisms of the development of nephritis in these mice, CD4+ T cells proliferating in their spleen were analyzed. Compared to controls, Irf4-/-MRL/lpr had significantly increased numbers of IFN-γ producing Th1-type cells, and significantly increased numbers of CD62L+/CD44+ memory CD4+ T cells and CD62L-/CD44+ effector CD4+ T cells. Similar results were observed in Irf4-/-NZM2410 mice, another murine lupus model. These results suggest that Irf4 associate with the development of IFN-γ producing memory and effector Th1 cells, and the association of these cells with the development of non-IC-dependent lupus-like glomerulonephritis observed in Irf4-deficient murine models of human SLE.

  • Research Products

    (7 results)

All 2011 2010 2009

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (5 results) Book (1 results)

  • [Journal Article] Comment on "Reassessment of the role of mut S homolog 5 in Ig class switch recombination shows lack of involvement in cis- and trans-switching".2009

    • Author(s)
      Sekine H, Ferreira RC, Pan-Hammarstrom Q, Hammarstrom L, Gilkeson GS, Behrens TW.
    • Journal Title

      J Immunol 182

      Pages: 496-497

    • Peer Reviewed
  • [Presentation] IRF4-Deficient lupus-prone MRL/lpr Mice lack serum Ig/auto-Abs and Th17 cells but develop non-immune complex-mediated diffuse proliferative glomerulonephritis and dermatitis/ear necrosis, American College of Rheumatology2010

    • Author(s)
      関根英治
    • Organizer
      74^<th> Annual Scientific Meeting
    • Place of Presentation
      Atlanta, USA
    • Year and Date
      2010-11-08
  • [Presentation] ループス腎炎と補体・補体第2経路を特異的に標的とする治療戦略2010

    • Author(s)
      関根英治
    • Organizer
      第47回 補体シンポジウム
    • Place of Presentation
      福島
    • Year and Date
      2010-09-10
  • [Presentation] IRF4-deficient lupus-prone MRL/lpr mice lack serum immunoglobulin and glomerular immune complex/C3 deposits but develop diffuse proliferative glomerulonephritis and dermatitis/ear necrosis2010

    • Author(s)
      関根英治
    • Organizer
      14^<th> International Congress of Immunology
    • Place of Presentation
      Kobe, Japan
    • Year and Date
      2010-08-23
  • [Presentation] Targeted inhibition of the alternative pathway ameliorates progression of renal disease in murine models of systemic lupus erythematosus2010

    • Author(s)
      関根英治
    • Organizer
      XXIII International Complement Workshop
    • Place of Presentation
      New York, USA
    • Year and Date
      2010-08-03
  • [Presentation] 転写因子IRF4欠損SLEモデルマウスが示唆するループス腎炎の新たなメカニズム2010

    • Author(s)
      関根英治
    • Organizer
      Rheumatology Conference 2010
    • Place of Presentation
      東京
    • Year and Date
      2010-06-26
  • [Book] 補体への招待2011

    • Author(s)
      関根英治
    • Total Pages
      88-94
    • Publisher
      メジカルビュー社

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Published: 2012-01-26   Modified: 2016-04-21  

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