2004 Fiscal Year Final Research Report Summary
Functional analysis of a novel inhibitory receptor expressed on plasmacytoid dendritic cells
| Project/Area Number |
15590432
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | International Medical Center of Japan |
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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)
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| Project Period (FY) |
2003 – 2004
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| Keywords | inhibitory receptor / plasmacytoid dendritic cell / NK receptor / differentiation marker / mouse |
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| 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
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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
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[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.
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Journal Title
J.Immunol. 74
Pages: 4621-4629
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
J Exp Med. 201
Pages: 333-339
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
Immunology
Pages: 187-191
Description
「研究成果報告書概要(欧文)」より
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[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.
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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
