Brd4 modulates the innate immune response through Mnk2–eIF4E pathway-dependent translational control of IκBα

著者: Yan Bao, Xuewei Wu, Jinjing Chen, Xiangming Hu, Fuxing Zeng, Jianjun Cheng, Hong Jin, Xin Lin, Lin‐Feng Chen - Proceedings of the National Academy of Sciences, PNAS 2017 被引用: 85

Significance We generated myeloid lineage-specific Brd4 conditional-knockout mice and demonstrated the critical role of Brd4 in the innate immune response in vivo. Brd4 CKO mice were resistant to LPS-induced sepsis but were more susceptible to bacterial infection. Deletion of Brd4 in macrophages decreased the TLR-mediated inflammatory cytokine expression. We also uncovered a mechanism by which Brd4 regulates the NF-κB signaling via initiation of translation. In response to LPS stimulation, deletion of Brd4 in macrophages led to the sustained expression of Mknk2 and the enhanced activation of eIF4E, which stimulates the translation of IκBα mRNA, resulting in decreased NF-κB–dependent inflammatory gene expression and compromised innate immune response.