MNK2 governs the macrophage antiinflammatory phenotype

Margarita Bartish, Dongmei Tong, Yangxun Pan, Majken Wallerius, Hui Liu, Johannes Ristau, Sabrina de Souza Ferreira, Tatjana Wallmann, Vincent van Hoef, Laia Masvidal, Thomas Kerzel, Anne Laure Joly, Christophe Goncalves, Samuel E.J. Preston, Talin Ebrahimian, Christina Seitz, Jonas Bergh, Kristian Pietras, Stephanie Lehoux, Luigi NaldiniJohn Andersson, Mario Leonardo Squadrito, Sonia V. del Rincón, Ola Larsson, Charlotte Rolny

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)27556-27565
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number44
DOIs
Publication statusPublished - Nov 3 2020

Keywords

  • EIF4E
  • MNK2
  • MRNA translation
  • T cell activation
  • Tumor-associated macrophages

ASJC Scopus subject areas

  • General

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