Effect of depletion of PERK on gene expression in T cells after polyclonal or allogeneic stimulation

PERK differentially regulates T cell allogeneic and anti-tumor responses. To further elucidate the mechanism, we performed transcriptomics analyses via bulk RNA sequencing on WT and PERK-deficient T cells after polyclonal or allogeneic stimulation. We here report that endoplasmic reticulum-associated degradation (ERAD)-associated genes, including Sel1l and Erlec1, were significantly increased in PERK conditional knock out (cKO) compared with WT T cells upon allogeneic but not polyclonal stimulation. SEL1L-HRD1 axis plays a central role in ERAD pathway, we also observed that PERK binds to SEL1L in activated human T-cell line. By using PERK-/-SEL1L-/- mice, we eluciated that PERK regulates T-cell allogeneic responses and GVHD induction through SEL1L-mediated ERAD pathway. Overall design: RNA-seq profiling of wildtype or PERK-deficient T cells after stimulation with anti-CD3 and anti-CD28 antibodies for 3 days or allogeneic antigen presenting cells (APCs) for 4 days.