TY - JOUR
T1 - MNK2 governs the macrophage antiinflammatory phenotype
AU - Bartish, Margarita
AU - Tong, Dongmei
AU - Pan, Yangxun
AU - Wallerius, Majken
AU - Liu, Hui
AU - Ristau, Johannes
AU - de Souza Ferreira, Sabrina
AU - Wallmann, Tatjana
AU - van Hoef, Vincent
AU - Masvidal, Laia
AU - Kerzel, Thomas
AU - Joly, Anne-Laure
AU - Goncalves, Christophe
AU - Preston, Samuel E.J.
AU - Ebrahimian, Talin
AU - Seitz, Christina
AU - Bergh, Jonas
AU - Pietras, Kristian
AU - Lehoux, Stephanie
AU - Naldini, Luigi
AU - Andersson, John
AU - Squadrito, Mario Leonardo
AU - Del Rincón, Sonia V.
AU - Larsson, Ola
AU - Rolny, Charlotte
PY - 2020/11/3
Y1 - 2020/11/3
N2 - 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.
AB - 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.
KW - eIF4E
KW - MNK2
KW - mRNA translation
KW - T cell activation
KW - tumor-associated macrophages
U2 - 10.1073/pnas.1920377117
DO - 10.1073/pnas.1920377117
M3 - Article
C2 - 33077599
AN - SCOPUS:85095670088
SN - 1091-6490
VL - 117
SP - 27556
EP - 27565
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 44
ER -