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p38α regulates cytokine‐induced IFNγ secretion via the Mnk1/eIF4E pathway in Th1 cells
Author(s) -
SalvadorBernáldez María,
Mateus Sara B,
Del Barco Barrantes Iván,
Arthur Simon C,
MartínezA Carlos,
Nebreda Angel R,
Salvador Jesús M
Publication year - 2017
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2017.51
Subject(s) - p38 mitogen activated protein kinases , microbiology and biotechnology , cytokine , secretion , biology , tumor necrosis factor alpha , t cell , protein kinase a , immune system , kinase , immunology , endocrinology
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 interferon (IFN)γ and tumor necrosis factor (TNF)α 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.