Hayakawa, MorisadaHayakawa, HirokoPetrova, TsvetanaRitprajak, PatchareeSutavani, Ruhcha V.Jiménez-Andrade, Guillermina YanekSano, YasuyoChoo, Min-KyungSeavitt, JohnVenigalla, Ram K. C.Otsu, KinyaGeorgopoulos, KatiaArthur, J. Simon C.Park, Jin Mo2017-03-282017Hayakawa, M., H. Hayakawa, T. Petrova, P. Ritprajak, R. V. Sutavani, G. Y. Jiménez-Andrade, Y. Sano, et al. 2017. “Loss of Functionally Redundant p38 Isoforms in T Cells Enhances Regulatory T Cell Induction*.” The Journal of Biological Chemistry 292 (5): 1762-1772. doi:10.1074/jbc.M116.764548. http://dx.doi.org/10.1074/jbc.M116.764548.http://nrs.harvard.edu/urn-3:HUL.InstRepos:31731785The 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 p38α, the ubiquitously expressed p38 isoform, showed no readily apparent cell-autonomous defects while expressing elevated amounts of another isoform, p38β. Mice with T cells simultaneously lacking p38α and p38β displayed lymphoid atrophy and elevated Foxp3+ regulatory T cell frequencies. Double deficiency of p38α and p38β in naïve 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.en-USimmunologymousep38signal transductionT-cellJournal Article2017-03-2810.1074/jbc.M116.764548