| First Author | Hayakawa M | Year | 2017 |
| Journal | J Biol Chem | Volume | 292 |
| Issue | 5 | Pages | 1762-1772 |
| PubMed ID | 28011639 | Mgi Jnum | J:240712 |
| Mgi Id | MGI:5888964 | Doi | 10.1074/jbc.M116.764548 |
| Citation | Hayakawa M, et al. (2017) Loss of Functionally Redundant p38 Isoforms in T Cells Enhances Regulatory T Cell Induction. J Biol Chem 292(5):1762-1772 |
| abstractText | 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 p38alpha, the ubiquitously expressed p38 isoform, showed no readily apparent cell-autonomous defects while expressing elevated amounts of another isoform, p38beta. Mice with T cells simultaneously lacking p38alpha and p38beta displayed lymphoid atrophy and elevated Foxp3+ regulatory T cell frequencies. Double deficiency of p38alpha and p38beta 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. |
