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

Journal of immunology (Baltimore, Md. : 1950) 2020 May 01

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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. Copyright © 2020 by The American Association of Immunologists, Inc.

Citation

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. 4E-BP-Dependent Translational Control of Irf8 Mediates Adipose Tissue Macrophage Inflammatory Response. Journal of immunology (Baltimore, Md. : 1950). 2020 May 01;204(9):2392-2400