Abstract
The kinase TAK1 is critical for innate and B cell immunity. The function of TAK1 in T cells is unclear, however. We show here that T cell-specific deletion of the gene encoding TAK1 resulted in reduced development of thymocytes, especially of regulatory T cells expressing the transcription factor Foxp3. In mature thymocytes, TAK1 was required for interleukin 7-mediated survival and T cell receptor-dependent activation of transcription factor NF-kappaB and the kinase Jnk. In effector T cells, TAK1 was dispensable for T cell receptor-dependent NF-kappaB activation and cytokine production, but was important for proliferation and activation of the kinase p38 in response to interleukins 2, 7 and 15. Thus, TAK1 is essential for the integration of T cell receptor and cytokine signals to regulate the development, survival and function of T cells.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation / immunology
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Cell Survival / immunology
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Flow Cytometry
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Immunoblotting
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Lymphocyte Activation / immunology
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MAP Kinase Kinase 4 / immunology
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MAP Kinase Kinase 4 / metabolism
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MAP Kinase Kinase Kinases / immunology*
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MAP Kinase Kinase Kinases / metabolism
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Mice
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Mice, Transgenic
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NF-kappa B / immunology
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NF-kappa B / metabolism
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Receptors, Antigen, T-Cell / immunology*
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Receptors, Antigen, T-Cell / metabolism
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Receptors, Cytokine / immunology*
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Receptors, Cytokine / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / immunology*
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T-Lymphocytes / cytology*
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T-Lymphocytes / immunology
Substances
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NF-kappa B
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Receptors, Antigen, T-Cell
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Receptors, Cytokine
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MAP Kinase Kinase Kinases
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MAP kinase kinase kinase 7
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MAP Kinase Kinase 4