Abstract
IRAK-4 is a protein kinase that is pivotal in mediating signals for innate immune responses. Here, we report that IRAK-4 signaling is also essential for eliciting adaptive immune responses. Thus, in the absence of IRAK-4, in vivo T cell responses were significantly impaired. Upon T cell receptor stimulation, IRAK-4 is recruited to T cell lipid rafts, where it induces downstream signals, including protein kinase C activation through the association with Zap70. This signaling pathway was found to be required for optimal activation of nuclear factor kappaB. Our findings suggest that T cells use this critical regulator of innate immunity for the development of acquired immunity, suggesting that IRAK-4 may be involved in direct signal cross talk between the two systems.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Enzyme Activation
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Immunity, Innate
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Interleukin-1 Receptor-Associated Kinases
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Isoenzymes / metabolism
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Lymphocyte Activation*
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Membrane Microdomains / enzymology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Transgenic
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NF-kappa B / metabolism
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Phosphotransferases (Alcohol Group Acceptor) / genetics
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Phosphotransferases (Alcohol Group Acceptor) / metabolism*
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Protein Kinase C / metabolism
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Protein Kinase C-theta
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Receptors, Antigen, T-Cell / immunology
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Signal Transduction
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T-Lymphocytes / immunology*
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ZAP-70 Protein-Tyrosine Kinase / metabolism
Substances
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Isoenzymes
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NF-kappa B
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Receptors, Antigen, T-Cell
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Phosphotransferases (Alcohol Group Acceptor)
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ZAP-70 Protein-Tyrosine Kinase
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Zap70 protein, mouse
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Interleukin-1 Receptor-Associated Kinases
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Irak4 protein, mouse
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Prkcq protein, mouse
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Protein Kinase C
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Protein Kinase C-theta