p38α regulates cytokine-induced IFNγ secretion via the Mnk1/eIF4E pathway in Th1 cells

María Salvador-Bernáldez, Sara B. Mateus, Iván Del Barco Barrantes, Simon C. Arthur, Carlos Martínez-A, Angel R. Nebreda, Jesús M. Salvador (Lead / Corresponding author)

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9 Citations (Scopus)

Abstract

The p38 mitogen-activated protein kinase (MAPK) pathway is involved in the regulation of immune and inflammatory processes. We used p38α-conditional, p38β-deficient, and p38α/β double-null mouse models to address the role of these two p38 MAPK in CD4(+) T cells, and found that p38α deficiency causes these cells to hyperproliferate. Our studies indicate that both p38α and p38β are dispensable for T helper cell type 1 (Th1) differentiation but, by controlling IFNγ and TNFα production, are critical for normal Th1 effector function. We found that both p38α and p38β modulate T cell receptor-induced IFNγ and TNFα production, whereas only p38α regulates cytokine-induced IFNγ production. The lack of p38α and p38β did not affect transcription and mRNA stability of Ifng. However, the absence of p38α in Th1 cells resulted in a decreased MNK1 phosphorylation after cytokine activation, and MNK1 inhibition blocked IFNγ production. Our results indicate that p38α regulates IFNγ secretion through the activation of the MNK1/eIF4E pathway of translation initiation and identify specific functions for p38α and p38β in T cell proliferation.Immunology and Cell Biology accepted article preview online, 14 June 2017. doi:10.1038/icb.2017.51.

Original languageEnglish
Pages (from-to)814-823
Number of pages10
JournalImmunology and Cell Biology
Volume95
Early online date14 Jun 2017
DOIs
Publication statusPublished - 14 Jun 2017

Keywords

  • Journal article

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    Salvador-Bernáldez, M., Mateus, S. B., Del Barco Barrantes, I., Arthur, S. C., Martínez-A, C., Nebreda, A. R., & Salvador, J. M. (2017). p38α regulates cytokine-induced IFNγ secretion via the Mnk1/eIF4E pathway in Th1 cells. Immunology and Cell Biology, 95, 814-823. https://doi.org/10.1038/icb.2017.51