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4E-BP-Dependent Translational Control of Irf8 Mediates Adipose Tissue Macrophage Inflammatory Response

Pearl, Dana, Katsumura, Sakie, Amiri, Mehdi, Tabatabaei, Negar, Zhang, Xu, Vinette, Valérie, Pang, Xinhe, Beug, Shawn T, Kim, Sung-Hoon, Jones, Laura M, Robichaud, Nathaniel, Ong, Sang-Ging, Jia, Jian-Jun, Ali, Hamza, Tremblay, Michel L, Jaramillo, Maritza ORCID: https://orcid.org/0000-0002-1910-5684, Alain, Tommy, Morita, Masahiro, Sonenberg, Nahum et Tahmasebi, Soroush (2020). 4E-BP-Dependent Translational Control of Irf8 Mediates Adipose Tissue Macrophage Inflammatory Response Journal of Immunology , vol. 204 , nº 9. p. 2392-2400. DOI: 10.4049/jimmunol.1900538.

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Résumé

Deregulation of mRNA translation engenders many human disorders, including obesity, neurodegenerative diseases, and cancer, and is associated with pathogen infections. The role of eIF4E-dependent translational control in macrophage inflammatory responses in vivo is largely unexplored. In this study, we investigated the involvement of the translation inhibitors eIF4E-binding proteins (4E-BPs) in the regulation of macrophage inflammatory responses in vitro and in vivo. We show that the lack of 4E-BPs exacerbates inflammatory polarization of bone marrow-derived macrophages and that 4E-BP-null adipose tissue macrophages display enhanced inflammatory gene expression following exposure to a high-fat diet (HFD). The exaggerated inflammatory response in HFD-fed 4E-BP-null mice coincides with significantly higher weight gain, higher Irf8 mRNA translation, and increased expression of IRF8 in adipose tissue compared with wild-type mice. Thus, 4E-BP-dependent translational control limits, in part, the proinflammatory response during HFD. These data underscore the activity of the 4E-BP-IRF8 axis as a paramount regulatory mechanism of proinflammatory responses in adipose tissue macrophages.

Type de document: Article
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 15 juill. 2021 00:54
Dernière modification: 15 févr. 2022 18:19
URI: https://espace.inrs.ca/id/eprint/11511

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