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A study of molecular pathology in experimental Sjogren's syndrome in mice

Research Project

Project/Area Number 08407057
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionThe University of Tokushima

Principal Investigator

HAYASHI Yoshio  The University of Tokushima, School of Dentistry, Professor, 歯学部, 教授 (00127854)

Co-Investigator(Kenkyū-buntansha) YANAGAI Kumiko  The University of Tokushima, School of Dentistry, Research Associate, 歯学部, 助手 (90294701)
HANEJI Norio  The University of Tokushima, School of Dentistry, Research Associate, 歯学部, 助手 (30274228)
中村 隆範  香川医科大学, 教授 (70183887)
浜野 弘規  徳島大学, 歯学部, 助手 (10238074)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥37,100,000 (Direct Cost: ¥37,100,000)
Fiscal Year 1998: ¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1997: ¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1996: ¥22,700,000 (Direct Cost: ¥22,700,000)
KeywordsSjogren syndrome / Animal model / NFS / sld mouse / Autoantigen / Autoreactive T cells / T cell epitope / B cell epitope / alpha-fodrin / アポトーシス / Fas抗原 / Bcl-2フアミリー / シェ-グレン症候群 / Sjogren's syndrome / Animal model / Autoantigen / α-fodrin / Fusion protein / Apoptosis / Cleavage / Therapeutic effect
Research Abstract

Primary Sjogren syndrome (SS) in humans is an autoimmune disease characterized by diffuse lymphoid cell infiltrates in the salivary and lacrimal glands, resulting in symptoms of dry mouth and dry eye clue to insufficient secretion. The spectrum of presentation of the disease is broad, ranging from the organ-localized dysfunction of exocrine gland to systemic complications such as liver, kidney and lung involvement. Moreover, a significant proportion of the SS patients may develop malignant lymphoproloferative disorders such as B cell lymphoma and macroglobulinemia. Although it has been assumed that a combination of immunologic, genetic, and environmental factors may play a key role on the development of autoimmune lesion in the salivary and lacrimal gland, little is known about the disease pathogenesis of primary SS in humans. A great interest is to investigate different immunological aspects of human autoimmune diseases including SS.The hypofunction of the salivary glands is due to lymphocytic infiltration, in which it is generally assumed that autoreactive T cells recognize unknown self-antigen and play a central role in the pathogenesis of SS.Primary SS is also characterized by systemic production of autoantibodies to ribonucleoprotein (RNP) particles SS-A/Ro and SS-B/ La, but the specificity for the immunogenicity of SS-A and SS-B remains unclear. Although it has been unclear whether or not there are critical organ-specific autoantigen(s) relevant to human primary SS, we have recently identified the 120KD alpha-fodrin as an important salivary gland autoantigen on the development of SS in both animal model and SS patients.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] N.Haneji et al: "Identification of α-fodrin as a candidate autoantigen in primary Sjogren's syndrome." Science. 276. 604-607 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Azuma et al: "Role of cytokines of acinar structure in Sjogren's syndrome salivary glands." Lab.Invest.77(3). 269-280 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Yaagi et al: "Anti-120-kDa α-fodrin immune response with Th-1-cytokine profile in the NOD mouse model of Sjogren's syndrome." Eur.J.Immunol.28. 3336-3345 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Tsubota et al: "Use of topical cyclosporin A in a primary Sjogren's syndrome mouse model." Invest.Ophthalmol.Vis.Sci.39. 1551-1559 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Miyagawa et al: "Neonatal lupus erythematosus:Maternal IgG antibodies bind to a recombinant NH2-terminal fusion protein encoded by human α-fodrin cDNA." J.Invest.Dermatol.111. 1189-1192 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Hayashi: "The immunology of Sjogren's syndrome:emphasis on the role of salivary gland autoantigen." Biomedical Reviews. in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] N.Haneji et al.: "Identification of alpha-fodrin as a candidate autoantigen in primary Sjogren's syndrome." Science. 276. 604-607 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Azuma et al.: "Role of cytokines of acinar structure in Sjogren's syndrome salivary glands." Lab. Invest.77 (3). 269-280 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Yanagi et al.: "Anti-120-kDa alpha-fodrin immune response with Th-1-cytokine profile in the NOD mouse model of Sjogren's syndrome" Eur. J.Immunol. 28. 3336-3345 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Tsubota et al.: "Use of topical cyc1osporin A in a primary Sjogren's syndrome mouse model." Invest. Ophthalmol. Vis. Sci.39. 1551-1559 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Miyagawa et al.: "Neonatal lupus erythematosus : Maternal IgG antibodies bind to a recombinant NH2-terminal fusion protein encoded by human alpha-fodrin cDNA." J.Invest. Dermatol.111. 1189-1192 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Hayashi: "The immunology of Sjogren's syndrome : emphasis on the role of salivary gland autoantigen." Biomedical Reviews. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Yanagi et al: "Anti-120-kDa α-fodrin immune response withTh-1-cytokine profile in the NOD mouse model of Sjogren's syndrome." Eur.J.Immunol.28. 3336-3345 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Tsubota et al: "Use of topical cyclosporin A in a primary Sjogren's syndrome mouse model." Invest.Ophthalmol.Vis.Sci.39. 1551-1559 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Miyagawa et al: "Neonatal lupus erythematosus:Maternal IgG antibodies bind to a recombinant NH2-terminal fusion protein encoded by human α-fodrin cDNA." J.Invest.Dermatol.111. 1189-1192 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Watanabe et al: "Anti-α-fodrin antibodies in Sjogren's syndrome and lupus erythematosus." Arch.Dermatol.(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Hayashi: "The immunology of Sjogren's syndrome:emphasis on the role of salivary gland autoantigen." Biomedical Reviews. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Takahashi et al: "Requirement for splenic CD4+ T cells in the immune privilege of the anterior chamber of the eye." Clin.Exp.Immunol.(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] N.Haneji et al: "Identification of α-fodrin as a candidate autoantigen in primary Sjogren's syndrome." Science. 276. 604-607 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] N.Ishimaru et al: "Accelerated onset of age-related autoimmune lesions in MRL/+ mice." Mech.Age.Develop.93. 145-156 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Takahashi et al: "High incidence of autoimmune dacryoadenitis in male non-obese diabetic (NOD) mice depending on sex steroid." Clin.Exp.Immunol.109. 555-561 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Yanagi et al: "Analysis of T cell receptor Vβ usage in the autoimmune sialadenitis of non-obese diabetic (NOD) mice." Clin.Exp.Immunol.110. 440-446 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Azuma et al: "Role of cytokines of acinar structure in Sjogren's syndrome salivary glands." Lab.Invest.77・3. 269-280 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 林 良夫: "Sjogren症候群疾患モデルと臓器特異的自己抗原" Molecular Medicine. 34・11. 1425-1429 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshio Hayashi et al.: "Effector mechanism of experimental autoimmune sialadenitis in the mouse model for primary Siogren's syndrome" Cell.Immunol.171. 217-225 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yoshio Hayashi et al.: "Cytokine gene expression and autoantibody production in Sjogeren's syndrome in MRL/lpr mice" Autoimmunity. 23. 269-277 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Mariko Takahashi et al.: "Mechanism of the development of autoimmune dacryoadenitis in the mouse model for primary Sjogren's syndrome" Cell.Immunol.170. 54-62 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yoshio Hayashi: "Cytokine,adhesion molecules,and immune deviation in autoimmune salivary gland disease" Oral Med.Pathol.1(1). 3-10 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kumiko Yanagi et al.: "In vivo role IL-10 and IL-12 during development of Sjogren's syndrome in MRL/lpr mice" Cell.Immunol.168. 243-250 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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