Abstract
NKT cells are known to rapidly produce a large amount of cytokines upon activation. Although a number of signaling pathways that regulate the development of NKT cells have been identified, the signaling pathways involved in the regulation of NKT cell cytokine production remain unclear. In this study, we show that the p38 MAPK pathway is dispensable for the development of NKT cells. However, NKT cell cytokine production and NKT-mediated liver damage are highly dependent on activation of this pathway. p38 MAPK does not substantially affect cytokine gene expression in NKT cells, but it regulates the synthesis of cytokines through the Mnk-eIF4E pathway. Thus, in addition to gene expression, translational regulation by p38 MAPK could be a novel mechanism that contributes to the overall production of cytokine by NKT cells.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cells, Cultured
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Cytokines / biosynthesis*
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Cytokines / genetics*
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Enzyme Activation / genetics
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Enzyme Activation / immunology
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Liver Diseases / enzymology
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Liver Diseases / genetics
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Liver Diseases / immunology
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MAP Kinase Kinase 3 / deficiency
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MAP Kinase Kinase 3 / genetics
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MAP Kinase Kinase 3 / physiology
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MAP Kinase Kinase 6 / deficiency
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MAP Kinase Kinase 6 / genetics
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MAP Kinase Kinase 6 / physiology
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MAP Kinase Signaling System / genetics
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MAP Kinase Signaling System / immunology*
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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, Knockout
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Mice, Transgenic
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Natural Killer T-Cells / enzymology
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Natural Killer T-Cells / immunology*
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Natural Killer T-Cells / metabolism*
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Protein Modification, Translational / immunology*
Substances
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Cytokines
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MAP Kinase Kinase 3
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MAP Kinase Kinase 6
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Map2k6 protein, mouse