H3K27ac Profiling in LIRIL2R-Deficient and LIRIL2R-Sufficient Induced Regulatory T Cells

Factors that determine the epigenetic landscape of regulatory T cells (Tregs), which is critical for their function, remain poorly understood. Long intergenic noncoding RNAs (LincRNA)s are important for shaping and maintaining the epigenetic landscape in different cell types. We identified a novel uncharacterised lincRNA, which we named LincRNA regulator of IL2RA (LIRIL2R), that is upregulated during early differentiation of human Tregs. RNA sequencing (RNA-seq) and data independent (DIA) proteomic analysis of LIRIL2R-deficient Tregs, with genome-wide chromatin occupancy analysis, identified IL2RA as direct LIRIL2R target. This nuclear lincRNA directly binds upstream of IL2RA locus and regulates its transcription by facilitating the accessibility of the locus. LIRIL2R-deficient Tregs had reduced expression of Treg-related genes, including FOXP3, IL2RA, STAT5, CTLA4 and PDCD1, as well as reduced suppressive capacity. Modulating LIRIL2R expression may hold promise for better therapeutic strategies against autoimmunity and cancer.