Counter-regulation of T cell effector function by differentially activated p38.

Type:Uv phototherapy   Time:2015-04-02 16:33:55
Counter-regulation of T cell effector function by differentially activated p38.
Alam MS1, Gaida MM1, Ogawa Y1, Kolios AG2, Lasitschka F3, Ashwell JD4.
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Abstract
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 p38¦Á and p38¦Â 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.
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