TY - JOUR
T1 - 4E-BP-dependent translational control of Irf8 mediates adipose tissue macrophage inflammatory response
AU - Pearl, Dana
AU - Katsumura, Sakie
AU - Amiri, Mehdi
AU - Tabatabaei, Negar
AU - Zhang, Xu
AU - Vinette, Valerie
AU - Pang, Xinhe
AU - Beug, Shawn T.
AU - Kim, Sung Hoon
AU - Jones, Laura M.
AU - Robichaud, Nathaniel
AU - Ong, Sang Ging
AU - Jia, Jian Jun
AU - Ali, Hamza
AU - Tremblay, Michel L.
AU - Jaramillo, Maritza
AU - Alain, Tommy
AU - Morita, Masahiro
AU - Sonenberg, Nahum
AU - Tahmasebi, Soroush
N1 - Publisher Copyright:
© 2020 by The American Association of Immunologists, Inc.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1900538
DO - 10.4049/jimmunol.1900538
M3 - Article
C2 - 32213561
AN - SCOPUS:85084065161
SN - 0022-1767
VL - 204
SP - 2392
EP - 2400
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -