Counter-regulation of T Cell Effector Function by Differentially Activated P38

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2014 May 28

PMID 24863062

Citations 27

Authors

Muhammad S Alam

Matthias M Gaida

Youichi Ogawa

Antonios G A Kolios

Felix Lasitschka

Jonathan D Ashwell

Affiliations

Soon will be listed here.

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 p38α and p38β 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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