Abstract
Cytohesin binder and regulator (Cybr) is known to regulate leukocyte adhesion and migration. However, its function in T-cells is poorly understood. Here, we investigated the role of Cybr in CD4(+) T-cell function and host immunity. Cybr inhibited p38 phosphorylation following CD4(+) T-cell stimulation. Since p38 regulates the expression of T-box expressed in T-cells (T-bet) but not GATA binding protein 3 (GATA-3) in T-cells, Cybr decreased the expression of T-bet and IFN-gamma in CD4(+) T-cells. Moreover, we found that host immunity against Listeria infection and IFN-gamma production in blood were significantly compromised in Cybr-overexpressing transgenic mice. In summary, our data suggest that Cybr represses the expression of T-bet and IFN-gamma via an inhibition of p38 in T-cells and consequently reduces host resistance to bacterial infection in mice.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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Carrier Proteins / immunology*
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Carrier Proteins / metabolism
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GATA3 Transcription Factor / biosynthesis
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GATA3 Transcription Factor / immunology
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Gene Expression Regulation / immunology*
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Interferon-gamma / biosynthesis
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Interferon-gamma / immunology*
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Listeria monocytogenes / immunology*
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Listeriosis / blood
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Listeriosis / immunology*
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Membrane Proteins / immunology*
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Membrane Proteins / metabolism
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Mice
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Phosphorylation / immunology
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T-Box Domain Proteins / biosynthesis
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T-Box Domain Proteins / immunology
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p38 Mitogen-Activated Protein Kinases / immunology
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Carrier Proteins
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Cybr protein, mouse
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GATA3 Transcription Factor
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Gata3 protein, mouse
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Membrane Proteins
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T-Box Domain Proteins
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T-box transcription factor TBX21
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Interferon-gamma
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p38 Mitogen-Activated Protein Kinases