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2003 Fiscal Year Final Research Report Summary

Identification of organ-specific cell surface molecules on T cells and endothelial cells in patients with systemic lupus erythematosus

Research Project

Project/Area Number 13470109
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionUniversity of Occupational and Environmental Health, Japan

Principal Investigator

TANAKA Yoshiya  University of Occupational & Environmental Health, Japan, School of Medicine, Professor, 医学部, 教授 (30248562)

Co-Investigator(Kenkyū-buntansha) OKADA Yosuke  University of Occupational & Environmental Health, Japan, School of Medicine, Assistant professor, 医学部, 講師 (80333243)
SAITO Kazuyoshi  University of Occupational & Environmental Health, Japan, School of Medicine, Assistant professor, 医学部, 講師 (30279327)
TSUKADA Junichi  University of Occupational & Environmental Health, Japan, School of Medicine, Associate professor, 医学部, 助教授 (20227367)
Project Period (FY) 2001 – 2003
Keywordssystemic lupus erythematosus / T cells / endothelial cells / integrin / co-stimulatory molecules / adhesion molecules / homing molecules / organ-tropism
Research Abstract

Systemic lupus erythematosus (SLE) is a representative autoimmune disease, which is involved in multiple organs such as skin, kidney, central nervous system, lung and so on, and sometimes results in severe prognosis. However, the precise pathological mechanisms of each organ involvement and specific treatments for them remain unclear. We have intensively studied the mechanism of circulating T cell migration into tissues through binding with endothelial cells. Recent progress in the field clarifies certain homing molecules on T cells and endothelial cells could define organ-specific homing of T cells. In this study, we first estimated the molecules on peripheral T cells in SLE patients with skin involvement. T cells, especially Th2 cells and Tc2 cells, of SLE with skin involvement characteristically highly expressed cutaneous lymphocyte-associated antigen (CLA), whereas T cells of SLE without skin lesion possessed marginal amounts of CLA, indicating that CLA might play a role in skin ra … More sh of SLE. Next, we assessed expression of specific gene on endothelial cells purified from skin, bone/bone marrow, lung, kidney, joint, thyroid and brain, using gene chip analyses. Each endothelial cells express very interesting genes and among them, for instance, endothelial cells from synovial membrane highly expressed CD40L, enkephalin, tetranectin, C1-inhibitor, CSF-1, IL-1R, SDF-1 and so on. Based on these chip analyses would warrant further studies in the context of organ-tropism. Finally, we assessed cell surface co-stimulatory molecules on SLE T cells. Interestingly, CD28 was reduced or decreased on active SLE T cells, whereas CD29 was highly up-regulated on them. When CD29 was crosslinked by specific antibodies, T cells were efficiently activated through FAK-tyrosine kinase and CD40L and CD69 were rapidly induced on the cells. Combined with other results, CD29 could play a potent role in SLE T cell activation, in an independent manner on CD28, resulting in organ involvement such as lupus nephritis. Taken together, to clarify the mechanisms of organ-tropic involvement in SLE, as shown in the study, could lead to more specific therapeutic approaches to SLE. Less

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Fujii K, Fujii Y, Hubscher S, Tanaka Y: "CD44 is the physiological trigger of Fas up-regulation on rheumatoid synovial calls."J Immunol. 167. 1198-1203 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka Y, Nakayamada S, Fujimoto H, Okada Y, Umehara H, Kataoka T, Minami Y: "H-Ras/mitogen-activated protein kinase pathway inhibits integrin-mediated adhesion and induces apoptosis in osteoblasts."J Biol Chem. 277. 21446-21452 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakayamada S, Saito K, Fujii K, Yasuda M, Tamura M, Tanaka Y.: "β1 integrin-mediated signaling induces ICAM-1 and Fas and Fas-mediated apoptosis of rheumatoid synovial calls."Arthritis Rheum. 48. 1239-1248 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakayamada S, Okada Y, Saito K, Tamura M, Tanaka Y.: "β1 integrin/focal adhesion kinase-mediated signaling induces intercellular adhesion molecule 1 and receptor activator of nuclear factor κB ligand on osteoblast and osteoclast maturation."J Biol Chem. 278. 45368-45374 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okada Y, Tsukada J, Nakano K, Tonai S, Mine S, Tanaka Y.: "Macrophage inflammatory protein-1 α induces hypercalcemia in adult T-cell leukemia."J Bone Miner Res. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakano K, Okada Y, Saito K, Tanaka Y.: "Fibroblast growth factor-2 induces receptor activator of nuclear factor kappa B ligand expression and osteoclast maturation by binding to heparan sulfate proteoglycan on rheumatoid synovial fibroblasts."Arthritis Rheum. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujii K, Fujii Y, Hubscher S, Tanaka Y: "CD44 is the physiological trigger of Fas up-regulation on rheumatoid synovial cells."J Immunol. 167. 1198-1203 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka Y, Nakayamada S, Fujimoto H, Okada Y, Umehara H, Kataoka T, Minami Y: "H-Ras/mitogen-activated protein kinase pathway inhibits integrin-mediated adhesion and induces apoptosis in osteoblasts."J Biol Chem. 277. 21446-21452 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakayamada S, Saito K, Fujii K, Yasuda M, Tamura M, Tanaka Y.: "β1 integrin-mediated signaling induces ICAM-1 and Fas and Fas-mediated apoptosis of rheumatoid synovial cells."Arthritis Rheum. 48. 1239-1248 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakayamada S, Okada Y, Saito K, Tamura M, Tanaka Y.: "β1 integrin/focal adhesion kinase-mediated signaling induces intercellular adhesion molecule 1 and receptor activator of nuclear factor κB ligand on osteoblast and osteoclast maturation."J Biol Chem. 278. 45368-45374 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okada Y, Tsukada J, Nakano K, Tonai S, Mine S, Tanaka Y.: "Macrophage inflammatory protein-1α induces hypercalcemia in adult T-cell leukemia."J Bone Miner Res. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakano K, Okada Y, Saito K, Tanaka Y.: "Fibroblast growth factor-2 induces receptor activator of nuclear factor kappa B ligand expression and osteoclast maturation by binding to heparan sulfate proteoglycan on rheumatoid synovial fibroblasts."Arthritis Rheum. (in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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