CD8 Effector T Cell Persistence in Atherosclerotic Plaque is Determined by Endothelial Elavl1/HuR

Here, we examine changes in translation of mRNA and alternatively spliced isoforms in low and disturbed flow (LDF) atherogenic endothelium via Translating Ribosome Affinity Purification (TRAP). We find ribosomal recruitment and alternative splicing of transcripts predicted to regulate T cell activation. We further show that the RNA-binding protein Embryonic Lethal, Abnormal Vision-Like 1 (Elavl1) is a critical component of the endothelial response in sites of chronic LDF, and that it is required for CD8 T cell accumulation in plaque. Motifs for Elavl1 are enriched nearby in alternatively spliced exons of the translatome, and the protein itself is increased in LDF endothelium. Cdh5(PAC)-CreERT2-mediated deletion of Elavl1 in the endothelium (ECKO) increased transcripts associated with phagocytosis and complement activity, including C1q, a key regulator of T cell responses.