Genomic analysis of long non-coding RNAs regulating Treg phenotypes in atherosclerosis 4498

Abstract Description Atherosclerosis is a chronic inflammatory disease of the arterial wall and the leading cause of global death. Regulatory T cells (Treg) play an important anti-atherogenic role. However, some Treg cells become exTregs, losing the immunosuppressive ability and exacerbating atherosclerosis. Identifying regulators of Treg phenotypes thus is crucial for understanding the disease etiology and improving therapies. Long non-coding RNAs (lncRNAs) are emerging as key regulator of gene expression and cell identify, yet their roles in Tregs remain poorly understood. Here, we de novel assembled the transcriptomes of sorted naïve, Treg and exTreg cells using public bulk RNA-seq datasets generated from 21 and 28 human and mouse samples. Our analysis identified over 900 previously unannotated human lncRNAs. Integrating GWAS dataset revealed 23 known and 18 novel lncRNAs harboring risk SNPs for coronary artery disease (CAD). Correlation analysis revealed that the expression of many lncRNAs significantly correlated with their neighboring protein-coding partners encoding transcription factors, cytokines, receptors and containing CAD SNPs. Differential analysis identified a list of known and novel lncRNAs that are dysregulated between different T cell populations, with 96 having mouse orthologs. Our findings suggest a critical role of lncRNAs in mediating Treg and exTreg phenotypes as well as the progression of atherosclerosis, providing a valuable resource for future functional studies. Funding Sources Supported by a Career Development Award (938570) from American Heart Association, start-up fund and Intramural Grants Program from Augusta University. Topic Categories Computational and Systems Immunology (COMP)