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Functional analysis of a novel inhibitory receptor expressed on plasmacytoid dendritic cells

Research Project

Project/Area Number 15590432
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionInternational Medical Center of Japan

Principal Investigator

TOYAMA Noriko  International Medical Center of Japan, Research Institute, 消化器疾患研究部消化管疾患研究室, 室長 (30217468)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsinhibitory receptor / plasmacytoid dendritic cell / NK receptor / differentiation marker / mouse / Ly49 / 樹状細胞 / IFNα
Research Abstract

Inhibitory receptors play crucial roles for fine regulation and termination of immune responses by negatively regulating cellular functions. A number of inhibitory receptors have been identified on various types of cells. In particular, inhibitory receptors on natural killer cells have been well characterized. It has been postulated that recognition of MHC class I, or related molecules, on target cells by inhibitory NK receptors allows NK cells to prevent self killing but destroy inappropriate cells possessing decreased levels of MHC class I.
Ly49Q is an ITIM-bearing inhibitory receptor belonging to Ly49 family that is known as one of subfamilies of NK receptors. Even though Ly49Q is classified into Ly49 family because of highly structural similarities and of its chromosomal location, Ly49Q has unique features different from other Ly49 family members. Ly49Q is not expressed on NK and NKT cells, but predominantly expressed on macrophages and plasmacytodi dendritic cells. Ly49Q has an abi … More lity to associate with both SHP-1 and SHP-2 in a tyrosine phosphorylation-dependent manner.
We here demonstrate that different expression levels of Ly49Q defined sequential maturational stages of PDCs in bone marrow. Moreover, we identified functionally different subsets of PDCs according to the expression of Ly49Q. Most CD11c^+B220^+PDCs in spleen and lymph node expressed high levels of Ly49Q. However, a significant portion of PDCs in BM, blood, liver and lung lacked Ly49Q expression. Ly49Q^- PDCs possessed lower abilities to produced IFN-αβ/, IL-6 and IL-12 p70 than Ly49Q^+ PDCs in response to TLR ligands. Interestingly, however, Ly49Q^- PDCs bore an ability to produce equivalent levels of TNF-α to Ly49Q^+ PDCs when exposed to CpG and HVJ. Thus, Ly49Q is a useful marker to reveal maturation process of PDCs and to distinguish functionally different subsets of PDCs. Our results suggest that cytokine profiles of PDCs alter during their maturational processes and that PDCs play different immunological functions depending on their maturational stages. To understand functional relevance of Ly49Q as well as MHC class I recognition by macrophages and dendritic cells, we started to establish transgenic mice expressing Ly49Q. Less

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (16 results)

All 2005 2004 Other

All Journal Article (13 results) Publications (3 results)

  • [Journal Article] Inhibitory NK receptor Ly49Q is expressed on subsets of dendritic cells in a cellular maturation- and cytokine stimulation-denendent manner.2005

    • Author(s)
      Toyama-Sorimachi, N., et al.
    • Journal Title

      J. Immunol. 174

      Pages: 4621-4629

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dok-1 and Dok-2 are negative regulators of lipopolysaccharide-induced signaling.2005

    • Author(s)
      Shinohara, H, et al.
    • Journal Title

      J Exp Med. 201

      Pages: 333-339

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inhibitory NK receptor Ly49Q is expressed on subsets of dendritic cells in a cellular maturation- and cytokine stimulation-dependen manner.2005

    • Author(s)
      Toyama-Sorimachi, N., Omatsu, Y., Onoda, A., Tsujimura, Y., Iyoda, T., Kikuchi-Maki, A., Sorimachi, H., Dohi, T., Taki, S., Inaba, K., Karasuyama, H.
    • Journal Title

      J.Immunol. 74

      Pages: 4621-4629

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dok-1 and Dok-2 are negative regulators of lipopolysaccharide-induced signaling.2005

    • Author(s)
      Shinohara H, Inoue A, Toyama-Sorimachi N.Nagai Y, Yasuda T, Suzuki H, Horai R, Iwakura Y, Yamamoto T, Karasuyama H, Miyake K, Yamanashi Y.
    • Journal Title

      J Exp Med. 201

      Pages: 333-339

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inhibitory NK receptor Ly49Q is expressed on subsets of dendritic cells in a cellular maturation- and cytokine stimulation-dependent manner.2005

    • Author(s)
      Toyama-Sorimachi, N.et al.
    • Journal Title

      J.Immunol. 74

      Pages: 4621-4629

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Dok-1 and Dok-2 are negative regulators of lipopolysaccharide-induced signaling.2005

    • Author(s)
      Shinohara H, et al.
    • Journal Title

      J Exp Med. 201

      Pages: 333-339

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Ly49Q1 is expressed on myeloid lineage cells and involved in regulation of cell adhesiveness.2004

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

      Immunology 2004

      Pages: 187-1911

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Ly49Q, a novel member of Ly49 family that is selectively, expressed on myeloid lineage cells and involved in regulation of cytoskeletal architecture.2004

    • Author(s)
      Toyama-Sorimachi, N., et al.
    • Journal Title

      Proc. Natl. Acad. Sci. USA. 101

      Pages: 1016-1021

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 樹状細胞における抑制性レセプターの役割2004

    • Author(s)
      反町典子
    • Journal Title

      臨床免疫 42

      Pages: 139-143

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Ly49Q1 is expressed on myeloid lineage cells and involved in regulation of cell adhesiveness.2004

    • Author(s)
      Tsujimra, Y., Kikuchi-Maki, A., Dohi, T., Onoda, A., Koyasu, S., Inaba, K, Karasuyama, H., Noriko Mama-Sorimachi
    • Journal Title

      Immunology

      Pages: 187-191

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Ly49Q, a novel member of Ly49 family that is selectively expressed on myeloid lineage cells and involved in regulation of cytoskeletal architecture.2004

    • Author(s)
      Toyama-Sorimachi, N., Tsujimura, Y., Maruya, M., Onoda, A., Kubota, T., Koyasu, S., Inaba, K., Karasuyama, H.
    • Journal Title

      Proc.Natl.Acad.Sci.USA. 101

      Pages: 1016-1021

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Ly49Q1 is expressed on myeloid lineage cells and involved in regulation of cell adhesiveness.2004

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

      Immunology 2004

      Pages: 187-191

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Ly49Q, a novel member of Ly49 family that is selectively expressed on myeloid lineage cells and involved in regulation of cytoskeletal architecture.2004

    • Author(s)
      Toyama-Sorimachi, N.et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA. 101

      Pages: 1016-1021

    • Related Report
      2004 Annual Research Report
  • [Publications] Noriko Toyama-Sorimachi, et al.: "Ly49Q, a member of the Ly49 family that is selectively expressed on myeloid lineage cells and involved in regulation of cytoskeletal architecture."Proc.Nati.Acad.Sci.USA. 101. 1016-1021 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Terauchi, M., et al.: "Placental extravillous cytotrophoblasts persistently express class I major histocom patibility complex molecules after human cytomegalovirus infection."J.Virol.. 77. 8187-8195 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 反町 典子: "免疫イラストマップ(分担執筆)"羊土社. 236 (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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