2007 Fiscal Year Final Research Report Summary
Positive and negative regulation of macrophage/ dendritic cell functions by novel paired receptors
| Project/Area Number |
18590256
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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 |
General medical chemistry
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| Research Institution | Gunma University |
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Principal Investigator |
OKAZAWA Hideki Gunma University, Institute for Molecular and Cellular Regulation, Assistant professor (80334126)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Dendritic cell / Macrophage / SHPS-1 / Phagocytosis / Cytokine |
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| Research Abstract |
SHPS-1 is a transmembrane protein that binds the protein tyrosine phosphatases SHP-1 and SHP-2 through its cytoplasmic region and is expressed on the surface of dendritic cells (DCs) and macrophages. We have now shown that forced expression in mouse RAW264.7 macrophages of a mutant version (SHPS-1-4F) of mouse SHPS-1, in which four tyrosine phosphorylation sites are replaced by phenylalanine, markedly promoted FcγR-mediated phagocytosis of mouse RBCs or SRBCs. In addition, expression of SHPS-1-4F promoted the production of TNFα and IL-6 induced by LPS or poly(I:C) in RAW cells. These data suggest that inhibition by SHPS-1 of phagocytosis in macrophages is mediated, at least in part, in a manner independent of the trans-interaction between CD47 and SHPS-1 and SHPS-1 negatively regulates TLR4- or TLR3- dependent cytokine production through inhibition of NFkB-dependent signaling.
We also show that mice that express a mutant form of SHPS-1 lacking most of the cytoplasmic region are resistant to experimental autoimmune encephalomyelitis (EAE) in response to immunization with a peptide derived from myelin oligodendrocyte glycoprotein [MOG(35-55)]. The MOG(35-55)-induced proliferation of, and production of IFN-γ, IL-2, and IL-17 by, T cells from immunized SHPS-1 mutant mice were reduced compared with those apparent for wild-type cells. These results show that SHPS-1 on DCs is essential for priming of naive T cells and the development of EAE. SHPS-1 is thus a potential therapeutic target in inflammatory disorders of the central nervous system and other autoimmune diseases.
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Research Products
(34 results)
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[Journal Article] Negative regulation by SHPS-1 of Toll-like receptor-dependent proinflammatory cytokine production in macrophages2008
Author(s)
Miyake, A., Murata, Y., Okazawa. H., Ikeda, H., Niwayama, Y., Ohnishi, H., Hirata, Y., Matozaki, T.
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Journal Title
Genes to Cells 13
Pages: 209-219
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Resistance to experimental autoimmune encephalomyelitis and impaired T cell priming by dendritic cells in Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 mutant mice2007
Author(s)
Tomizawa, T., Kaneko, Y., Kaneko, Y., Saito, Y., Ohnishi, H., Okajo, J., Okuzawa, C., Ishikawa-Sekigami, T., Murata, Y., Okazawa. H., Okamoto, K., Nojima, Y., Matozaki, T.
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Journal Title
Journal of Immunology 179
Pages: 869-877
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Regulation by Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 of α-Galactosylceramide-induced antimetastatic activity and Th1 and Th2 responses of NKT cells2007
Author(s)
Okajo, J., Kaneko, Y., Murata, Y., Tomizawa, T., Okuzawa, C., Saito, Y., Kaneko, Y., Ishikawa-Sekigami, T., Okazawa. H., Ohnishi, H., Matozaki, T., and Nojima, Y.
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Journal Title
Journal of Immunology 178
Pages: 6164-6172
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mutational analysis of the mechanism of negative regulation by Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 of phagocytosis in macrophages2006
Author(s)
Ikeda, H., Okazawa. H., Ohnishi, H., Murata, Y., Oldenborg, P. -A., and Matozaki, T.
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Journal Title
Journal of Immunology 177
Pages: 3123-3132
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 regulates the induction of Langerhans cell maturation2006
Author(s)
Fukunaga, A., Nagai, H., Yu, X., Oniki, S., Okazawa. H., Motegi, S., Suzuki, R., Honma, N., Matozaki, T., Nishigori, C., and Horikawa, T.
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Journal Title
European Journal of Immunology 3
Pages: 3216-3226
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Regulation by SHPS-1 of Toll-like receptor-mediated cytokine production by macrophages2007
Author(s)
Miyake, A., Murata, Y., Okazawa, H., Ikeda, H., Onhishi, H., Hirata, Y., Matozaki, T.
Organizer
BMB2007
Place of Presentation
Pacifico Yokohama
Year and Date
20071211-13
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Regulation by SHPS-1 of Toll-like receptor-mediated cytokine production by macrophages2007
Author(s)
Miyake, A., Murata, Y., Okazawa, H., Ikeda, H., Onhishi, H., Hirata, Y., Matozaki, T.
Organizer
The 37th annual meeting of the Japanese Society for Immunology
Place of Presentation
Tokyo
Year and Date
20071120-22
Description
「研究成果報告書概要(欧文)」より
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[Presentation] An essential role of SHPS-1 in proper development of dendritic cells for induction of Th17-mediated autoimmune diseases2007
Author(s)
Saito, Y., Kaneko, Y., Kaneko, Y., Okuzawa, C., Sekigami, T., Okajo, J., Tomizawa, T., Murata, Y., Okazawa, H., Onhishi, H., Matozaki, T., Nojima, Y.
Organizer
The 37th annual meeting of the Japanese Society for Immunology
Place of Presentation
Tokyo
Year and Date
20071120-22
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Regulation by SHPS-1 of skin immunity and of Toll-like receptor-mediated cytokine production2007
Author(s)
Motegi, S., Okazawa, H., Kobayashi, H., Murata, Y., Ohnishi, H., Ishikawa, O., Matozaki, T.
Organizer
The 37th annual meeting of the Japanese Society for Immunology
Place of Presentation
Tokyo
Year and Date
20071120-22
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Regulation by SHPS-1 of skin immunity and of Toll-like receptor-mediated cytokine production2007
Author(s)
Motegi, S., Okazawa, H., Kobayashi, H., Murata, Y., Ohnishi, H., Ishikawa, O., Matozaki, T.
Organizer
The 66th annual meeting of the Japanese Cancer Asociation
Place of Presentation
PacificoYokohama
Year and Date
20071003-05
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Negative regulation by SHPS-1 of Toll-like receptor-mediated cytokine production by macrophages2007
Author(s)
Miyake, A., Murata, Y., Okazawa, H., Ikeda, H., Niwayama, Y., Onhishi, H., Hirata, Y., Matozaki, T.
Organizer
The 6th Conference of Biofunctions
Place of Presentation
Hakone
Year and Date
20070922-23
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Negative regulation by SHPS-1 of Toll-like receptor mediated cytokine production by macrophages2007
Author(s)
Miyake, A., Murata, Y., Okazawa, H., Ikeda, H., Onhishi, H., Hirata, Y., Matozaki, T.
Organizer
EuroPhosphatases 2007 "Protein Phosphatases in Health and Disease"
Place of Presentation
Aveiro Portugal
Year and Date
20070724-28
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Roles of SHPS-1 and its family protein SIRPβ in regulation of macrophage phagocytosis2007
Author(s)
Okazawa, H., Motegi, S., Ikeda, H., Morimoto, N., Ishikawa-Sekigami, T., Hayashi, A., Murata, Y., Ohnishi, H., Matozaki, T.
Organizer
The 59th annual meeting of the Japan Society for Cell Biology The 40th annual mmeting of the Japanese Society of Developmental Biologists
Place of Presentation
Fukuoka
Year and Date
20070528-30
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Regulation by Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 of α-Galactosylceramide-induced antimetastatic activity and Th1 and Th2 responses of NKT cells2006
Author(s)
Okajo, J., Kaneko, Y., Murata, Y., Okazawa, H., Ohnishi, H., Nojima, Y., Matozaki, T.
Organizer
The 65th annual meeting of the Japanese Cancer Asociation
Place of Presentation
Pacifico Yokohama
Year and Date
20060928-30
Description
「研究成果報告書概要(欧文)」より
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