The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Kristian Pietras

Kristian Pietras

Research team manager

Kristian Pietras

MNK2 governs the macrophage antiinflammatory phenotype

Author

  • 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 Naldini
  • John Andersson
  • Mario Leonardo Squadrito
  • Sonia V. Del Rincón
  • Ola Larsson
  • Charlotte Rolny
Show all

Summary, in English

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.

Publishing year

2020-11-03

Language

English

Pages

27556-27565

Publication/Series

Proceedings of the National Academy of Sciences of the United States of America

Volume

117

Issue

44

Document type

Journal article

Publisher

National Academy of Sciences

Topic

  • Cancer and Oncology

Keywords

  • eIF4E
  • MNK2
  • mRNA translation
  • T cell activation
  • tumor-associated macrophages

Status

Published

ISBN/ISSN/Other

  • ISSN: 1091-6490