PERK is a critical metabolic hub for immunosuppressive function in macrophages

Here we report that the Th2 cytokine IL-4 and the tumor microenvironment activated protein kinase RNA-like ER kinase (PERK) stress signaling cascade to promote immunosuppressive M2 activation and proliferation. PERK activation mediated the upregulation of PSAT1 and serine biosynthesis via the downstream transcription factor ATF4. We found that Increased serine biosynthesis could result in enhanced mitochondrial function and a-ketoglutarate (a-KG) production required for JMJD3-dependent epigenetic modification. Overall design: Examination of H3K27me3 in WT and PERK-KO macrophages in different polarizing conditions. A total of 10 samples were included in the study. One sample from each WT and KO for naïve (M0) macrophages; two biological replicates from each WT and KO for M1 and M2 conditions.