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2005 Fiscal Year Final Research Report Summary

Analyses of the immunoregulatory mechanisms by IL-12-related cytokines and their receptors

Research Project

Project/Area Number 16390145
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionSaga University

Principal Investigator

YOSHIDA Hiroki  Saga University, Faculty of Medicine, Professor, 医学部, 教授 (40260715)

Project Period (FY) 2004 – 2005
KeywordsIL-27 / CD4+T cells / inflammation / Infection / autoimmunity / cytokines / Th1 / lymphocyte differentiation
Research Abstract

Cytokine/cytokine receptor network is critical in the establishment of immune reaction against various pathogens. We have generated a line of mice deficient for IL-27 receptor (WSX-1) gene and have proved that the mice show remarkable susceptibility against Leishmania major infection by impaired IFN-gamma production. By additional elucidation of the signal transduction mechanisms downstream of IL-27R, we have shown that IL-27/IL-27R (WSX-1) is critical in the initial commitment of Th1 differentiation, prior to IL-12. In addition, IL-27/WSX-1 is also shown to have immunoregulatory function by suppression of pro-inflammatory cytokine production during some protozoan infection. In the current study, we further analyzed the immunoregulatory roles of IL-27 and reported that, due to the augmented inflammatory responses in the absence of IL-27 signaling, allergic asthma exacerbated and also that lethal systemic inflammation occurred during Mycobacterium tuberculosis infection. In MRL/lpr mice, which develop human systemic lupus erythematosus-like autoimmune disease, lack of IL-27R was accompanied with membranous glomerulonephritis (MGN), instead of diffuse proliferative glomerulonephritis in the wild-type mice. To the best of our knowledge, this is the first presentation of a line of model mice that spontaneously develop MGN. For the dual roles of IL-27, we also examined the signal transduction mechanisms and have found that, for Th1 induction, STAT1 activation is critical and that, for immunoregulation, STAT3 activation is important ; further elucidation of the roles and mechanisms of IL-27 is required for therapeutic application of IL-27.

  • Research Products

    (22 results)

All 2006 2005 2004

All Journal Article (21 results) Book (1 results)

  • [Journal Article] Suppressor of cytokine signalling 1 in lymphocytes regulates the development of intestinal inflammation in mice.2006

    • Author(s)
      Inagaki-Ohara, K. et al.
    • Journal Title

      Gut 55

      Pages: 212-9

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Histological analyses of normally grown, fertile Apafl-deficient mice.2006

    • Author(s)
      Okamoto, H., Shiraishi, H., Yoshida, H.
    • Journal Title

      Cell Death Differ 13

      Pages: 668-71

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Suppressor of cytokine signalling 1 in lymphocytes regulates the development of intestinal inflammation in mice.2006

    • Author(s)
      Inagaki-Ohara, K.et al.
    • Journal Title

      Gut 55

      Pages: 212-219

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Histological analyses of normally grown, fertile Apaf1-deficient mice.2006

    • Author(s)
      Okamoto, H., Shiraishi, H., Yoshida, H.
    • Journal Title

      Cell Death Differ 13

      Pages: 668-671

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The IL-27 Receptor Chain WSX-1 Differentially Regulates Antibacterial Immunity and Survival during Experimental Tuberculosis.2005

    • Author(s)
      Holscher, C. et al.
    • Journal Title

      J Immunol 174

      Pages: 3534-44

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] WSX-1 over-expression in CD4+ T cells leads to hyperproliferation and cytokine hyperproduction in response to TCR stimulation.2005

    • Author(s)
      Takeda, A. et al.
    • Journal Title

      Int Immunol 17

      Pages: 889-97

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Exacerbation of Experimental Allergic Asthma by Augmented Th2 Responses in WSX-1-Deficient Mice.2005

    • Author(s)
      Miyazaki, Y. et al.
    • Journal Title

      J Immunol 175

      Pages: 2401-7

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Autoamplification of NFATcl expression determines its essential role in bone homeostasis.2005

    • Author(s)
      Asagiri, M. et al.
    • Journal Title

      J. Exp. Med. 202

      Pages: 1261-1269

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] T Helper 1-Inducing Property of IL-27/WSX-1 Signaling Is Required for the Induction of Experimental Colitis.2005

    • Author(s)
      Honda, K. et al.
    • Journal Title

      Inflatnm Bowel Dis 11

      Pages: 1044-1052

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Membranous Glomerulonephritis Development with Th2-Type Immune Deviations in MRL/lpr Mice Deficient for IL-27 Receptor (WSX-1).2005

    • Author(s)
      Shimizu, S. et al.
    • Journal Title

      J Immunol 175

      Pages: 1261-1269

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The IL-27 Receptor Chain WSX-1 Differentially Regulates Antibacterial Immunity and Survival during Experimental Tuberculosis.2005

    • Author(s)
      Holscher, C.et al.
    • Journal Title

      J Immunol 174

      Pages: 3534-3544

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] WSX-1 over-expression in CD4+ T cells leads to hyperproliferation and cytokine hyperproduction in response to TCR stimulation.2005

    • Author(s)
      Takeda, A.et al.
    • Journal Title

      Int Immunol 17

      Pages: 889-897

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Exacerbation of Experimental Allergic Asthma by Augmented Th2 Responses in WSX-1-Deficient Mice.2005

    • Author(s)
      Miyazaki, Y.et al.
    • Journal Title

      J Immunol 175

      Pages: 2401-2407

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Autoamplification of NFATc1 expression determines its essential role in bone homeostasis.2005

    • Author(s)
      Asagiri, M.et al.
    • Journal Title

      J.Exp.Med. 202

      Pages: 1261-1269

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] T Helper 1-Inducing Property of IL-27/WSX-1 Signaling Is Required for the Induction of Experimental Colitis.2005

    • Author(s)
      Honda, K.et al.
    • Journal Title

      Inflamm Bowel Dis 11

      Pages: 1044-1052

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Membranous Glomerulonephritis Development with Th2-Type Immune Deviations in MRL/lpr Mice Deficient for IL-27 Receptor (WSX-1).2005

    • Author(s)
      Shimizu, S.et al.
    • Journal Title

      J Immunol 175

      Pages: 7185-7192

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Hyperproduction of Proinflammatory Cytokines by WSX-1-Deficient NKT Cells in Concanavalin A-Induced Hepatitis.2004

    • Author(s)
      Yamanaka, A. et al.
    • Journal Title

      J Immunol 172

      Pages: 3590-3596

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] WSX-l : A Key Role in Induction of Chronic Intestinal Nematode Infection.2004

    • Author(s)
      Bancroft, A.J., et al.
    • Journal Title

      J Immunol 172

      Pages: 7635-41

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The IL-27 receptor (WSX-1) is an inhibitor of innate and adaptive elements of type 2 immunity.2004

    • Author(s)
      Artis, D. et al.
    • Journal Title

      J Immunol 173

      Pages: 5626-34

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] WSX-1 : A Key Role in Induction of Chronic Intestinal Nematode Infection.2004

    • Author(s)
      Bancroft, A.J., Humphreys, N.E., Worthington, J.J., Yoshida, H., Grencis, R.K.
    • Journal Title

      J Immunol 172

      Pages: 7635-7641

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The IL-27 receptor (WSX-1) is an inhibitor of innate and adaptive elements of type 2 immunity.2004

    • Author(s)
      Artis, D.et al.
    • Journal Title

      J Immunol 173

      Pages: 5626-5634

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Recent Res Devel Immunology : Research Signpost2004

    • Author(s)
      Yoshida, H., Hamano, S., Miyazaki, Y.
    • Total Pages
      12
    • Publisher
      The role of WSX-1 (IL-27R) as an initiator and attenuator of immune responses and inflammation.
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2007-12-13  

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