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) ER stress signaling cascade to promote immunosuppressive M2 activation and proliferation. Lacking PERK signaling impeded mitochondrial respiration and lipid oxidation critical for M2 macrophages. In addition, PERK activation mediated the upregulation of PSAT1 and serine biosynthesis via the downstream transcription factor ATF4. mRNA of IL-4-stimulated, or naïve bone marrow-derived macrophages from PERK WT or KO mice