Translational control of NKT cell cytokine production by p38 MAPK

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...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2011-04, Vol.186 (7), p.4140-4146
Main Authors: Nagaleekar, Viswas K, Sabio, Guadalupe, Aktan, Idil, Chant, Alan, Howe, Isaac W, Thornton, Tina M, Benoit, Patrick J, Davis, Roger J, Rincon, Mercedes, Boyson, Jonathan E
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation - genetics
Cell Differentiation - immunology
Cells, Cultured
Cytokines - biosynthesis
Cytokines - genetics
Enzyme Activation - genetics
Enzyme Activation - immunology
Liver Diseases - enzymology
Liver Diseases - genetics
Liver Diseases - immunology
MAP Kinase Kinase 3 - deficiency
MAP Kinase Kinase 3 - genetics
MAP Kinase Kinase 3 - physiology
MAP Kinase Kinase 6 - deficiency
MAP Kinase Kinase 6 - genetics
MAP Kinase Kinase 6 - physiology
MAP Kinase Signaling System - genetics
MAP Kinase Signaling System - immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Natural Killer T-Cells - enzymology
Natural Killer T-Cells - immunology
Natural Killer T-Cells - metabolism
Protein Modification, Translational - immunology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1002614