4E-BP-dependent translational control of Irf8 mediates adipose tissue macrophage inflammatory response

Dana Pearl, Sakie Katsumura, Mehdi Amiri, Negar Tabatabaei, Xu Zhang, Valerie Vinette, Xinhe Pang, Shawn T. Beug, Sung Hoon Kim, Laura M. Jones, Nathaniel Robichaud, Sang Ging Ong, Jian Jun Jia, Hamza Ali, Michel L. Tremblay, Maritza Jaramillo, Tommy Alain, Masahiro Morita, Nahum Sonenberg, Soroush Tahmasebi

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2392-2400
Number of pages9
JournalJournal of Immunology
Volume204
Issue number9
DOIs
StatePublished - May 1 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Pearl, D., Katsumura, S., Amiri, M., Tabatabaei, N., Zhang, X., Vinette, V., Pang, X., Beug, S. T., Kim, S. H., Jones, L. M., Robichaud, N., Ong, S. G., Jia, J. J., Ali, H., Tremblay, M. L., Jaramillo, M., Alain, T., Morita, M., Sonenberg, N., & Tahmasebi, S. (2020). 4E-BP-dependent translational control of Irf8 mediates adipose tissue macrophage inflammatory response. Journal of Immunology, 204(9), 2392-2400. https://doi.org/10.4049/jimmunol.1900538