Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 292, Issue 5, Pages 1762-1772Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M116.764548
Keywords
immunology; mouse; p38; signal transduction; T-cell
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Funding
- National Institutes of Health [AI074957]
- Medical Research Council
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The evolutionarily conserved protein kinase p38 mediates innate resistance to environmental stress and microbial infection. Four p38 isoforms exist in mammals and may have been co-opted for new roles in adaptive immunity. Murine T cells deficient in p38, the ubiquitously expressed p38 isoform, showed no readily apparent cell-autonomous defects while expressing elevated amounts of another isoform, p38. Mice with T cells simultaneously lacking p38 and p38 displayed lymphoid atrophy and elevated Foxp3(+) regulatory T cell frequencies. Double deficiency of p38 and p38 in naive CD4(+) T cells resulted in an attenuation of MAPK-activated protein kinase (MK)-dependent mTOR signaling after T cell receptor engagement, and enhanced their differentiation into regulatory T cells under appropriate inducing conditions. Pharmacological inhibition of the p38-MK-mTOR signaling module produced similar effects, revealing potential for therapeutic applications.
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