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Counter-regulation of T cell effector function by differentially activated p38
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-activ...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4042639/ https://www.ncbi.nlm.nih.gov/pubmed/24863062 http://dx.doi.org/10.1084/jem.20131917 |
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author | Alam, Muhammad S. Gaida, Matthias M. Ogawa, Youichi Kolios, Antonios G.A. Lasitschka, Felix Ashwell, Jonathan D. |
author_facet | Alam, Muhammad S. Gaida, Matthias M. Ogawa, Youichi Kolios, Antonios G.A. Lasitschka, Felix Ashwell, Jonathan D. |
author_sort | Alam, Muhammad S. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4042639 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-40426392014-12-02 Counter-regulation of T cell effector function by differentially activated p38 Alam, Muhammad S. Gaida, Matthias M. Ogawa, Youichi Kolios, Antonios G.A. Lasitschka, Felix Ashwell, Jonathan D. J Exp Med Article 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. The Rockefeller University Press 2014-06-02 /pmc/articles/PMC4042639/ /pubmed/24863062 http://dx.doi.org/10.1084/jem.20131917 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Alam, Muhammad S. Gaida, Matthias M. Ogawa, Youichi Kolios, Antonios G.A. Lasitschka, Felix Ashwell, Jonathan D. Counter-regulation of T cell effector function by differentially activated p38 |
title | Counter-regulation of T cell effector function by differentially activated p38 |
title_full | Counter-regulation of T cell effector function by differentially activated p38 |
title_fullStr | Counter-regulation of T cell effector function by differentially activated p38 |
title_full_unstemmed | Counter-regulation of T cell effector function by differentially activated p38 |
title_short | Counter-regulation of T cell effector function by differentially activated p38 |
title_sort | counter-regulation of t cell effector function by differentially activated p38 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4042639/ https://www.ncbi.nlm.nih.gov/pubmed/24863062 http://dx.doi.org/10.1084/jem.20131917 |
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