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MNK2 governs the macrophage antiinflammatory phenotype

Bartish, Margarita ; Tong, Dongmei ; Pan, Yangxun ; Wallerius, Majken ; Liu, Hui ; Ristau, Johannes ; de Souza Ferreira, Sabrina ; Wallmann, Tatjana ; van Hoef, Vincent and Masvidal, Laia , et al. (2020) In Proceedings of the National Academy of Sciences of the United States of America 117(44). p.27556-27565
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
eIF4E, MNK2, mRNA translation, T cell activation, tumor-associated macrophages
in
Proceedings of the National Academy of Sciences of the United States of America
volume
117
issue
44
pages
10 pages
publisher
National Academy of Sciences
external identifiers
  • pmid:33077599
  • scopus:85095670088
ISSN
1091-6490
DOI
10.1073/pnas.1920377117
language
English
LU publication?
no
id
46832332-ae71-41d5-a01d-1aedb21cb9ef
date added to LUP
2020-11-24 16:27:42
date last changed
2025-04-04 14:44:47
@article{46832332-ae71-41d5-a01d-1aedb21cb9ef,
  abstract     = {{<p>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.</p>}},
  author       = {{Bartish, Margarita and Tong, Dongmei and Pan, Yangxun and Wallerius, Majken and Liu, Hui and Ristau, Johannes and de Souza Ferreira, Sabrina and Wallmann, Tatjana and van Hoef, Vincent and Masvidal, Laia and Kerzel, Thomas and Joly, Anne-Laure and Goncalves, Christophe and Preston, Samuel E.J. and Ebrahimian, Talin and Seitz, Christina and Bergh, Jonas and Pietras, Kristian and Lehoux, Stephanie and Naldini, Luigi and Andersson, John and Squadrito, Mario Leonardo and Del Rincón, Sonia V. and Larsson, Ola and Rolny, Charlotte}},
  issn         = {{1091-6490}},
  keywords     = {{eIF4E; MNK2; mRNA translation; T cell activation; tumor-associated macrophages}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{44}},
  pages        = {{27556--27565}},
  publisher    = {{National Academy of Sciences}},
  series       = {{Proceedings of the National Academy of Sciences of the United States of America}},
  title        = {{MNK2 governs the macrophage antiinflammatory phenotype}},
  url          = {{http://dx.doi.org/10.1073/pnas.1920377117}},
  doi          = {{10.1073/pnas.1920377117}},
  volume       = {{117}},
  year         = {{2020}},
}