| First Author | Alam MS | Year | 2014 |
| Journal | J Exp Med | Volume | 211 |
| Issue | 6 | Pages | 1257-70 |
| PubMed ID | 24863062 | Mgi Jnum | J:214296 |
| Mgi Id | MGI:5588738 | Doi | 10.1084/jem.20131917 |
| Citation | Alam MS, et al. (2014) Counter-regulation of T cell effector function by differentially activated p38. J Exp Med 211(6):1257-70 |
| abstractText | Unlike the MAP kinase (MAPK) cascade that phosphorylates p38 on the activation loop, T cell receptor (TCR) signaling results in phosphorylation on Tyr-323 (pY323, alternative pathway). Using mice expressing p38alpha and p38beta with Y323F substitutions, we show that alternatively but not MAPK cascade-activated p38 up-regulates the transcription factors NFATc1 and IRF4, which are required for proliferation and cytokine production. Conversely, activation of p38 with UV or osmotic shock mitigated TCR-mediated activation by phosphorylation and cytoplasmic retention of NFATc1. Notably, UVB treatment of human psoriatic lesions reduced skin-infiltrating p38 pY323(+) T cell IRF4 and IL-17 production. Thus, distinct mechanisms of p38 activation converge on NFATc1 with opposing effects on T cell immunity, which may underlie the beneficial effect of phototherapy on psoriasis. |
