| Literature DB >> 33077599 |
Margarita Bartish1,2, Dongmei Tong1,2, Yangxun Pan1,2,3, Majken Wallerius1,2, Hui Liu1,2, Johannes Ristau1,2, Sabrina de Souza Ferreira1,2, Tatjana Wallmann1,2, Vincent van Hoef1,2, Laia Masvidal1,2, Thomas Kerzel4,5, Anne-Laure Joly6, Christophe Goncalves7, Samuel E J Preston8, Talin Ebrahimian8, Christina Seitz6, Jonas Bergh1, Kristian Pietras5, Stephanie Lehoux8, Luigi Naldini4,5, John Andersson6, Mario Leonardo Squadrito4,5, Sonia V Del Rincón7, Ola Larsson9,2, Charlotte Rolny9,2.
Abstract
Tumor-associated macrophages (TAMs) continuously fine tune their immune modulatory properties, but how gene expression programs coordinate this immune cell plasticity is largely unknown. Selective mRNA translation, controlled by MNK1/MNK2 and mTOR pathways impinging on eIF4E, facilitates reshaping of proteomes without changes in abundance of corresponding mRNAs. Using polysome profiling developed for small samples we show that, during tumor growth, gene expression in TAMs is predominately modulated via mRNA-selective changes in translational efficiencies. These alterations in gene expression paralleled accumulation of antiinflammatory macrophages with augmented phosphorylation of eIF4E, a target of the MNK1 and MNK2 kinases, known to selectively modulate mRNA translation. Furthermore, suppression of the MNK2, but not the mTOR signaling pathway, reprogrammed antiinflammatory macrophages toward a proinflammatory phenotype with the ability to activate CD8+ T cells. Thus, selective changes of mRNA translation depending on MNK2 signaling represents a key node regulating macrophage antiinflammatory functions.Entities:
Keywords: MNK2; T cell activation; eIF4E; mRNA translation; tumor-associated macrophages
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Year: 2020 PMID： 33077599 PMCID： PMC7959504 DOI： 10.1073/pnas.1920377117
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205