Differential long noncoding RNA signatures in activated plasmacytoid dendritic cells (IRM6P.659)

Abstract

Abstract Long noncoding RNAs (lncRNAs) represent a novel class of RNA which act through diverse mechanisms to exert control over a wide range of cellular processes. Through control of transcription, post-transcriptional regulation, or cellular signaling events, lncRNAs can function as potent modulators of innate immune responses, however very few lncRNAs have been investigated. We utilized whole exome sequencing of plasmacytoid dendritic cells (pDC) treated with IFN (interferon)-β, TLR7 agonist (toll like receptor, R848), and R848 with type I IFN blockade to identify 910 noncoding transcripts which are differentially regulated by IFN signaling and TLR7 activation. Through dissection of the stimulatory events controlling lncRNA expression, we have identified subsets of type I IFN- and TLR7-induced or suppressed lncRNAs. We hypothesize that many of these transcripts participate in the orchestration of innate and adaptive antiviral immunity through their modulation of pDC function. Dysregulation of these lncRNAs could significantly alter pDC maturation, IFN production, antigen presentation, turnover or localization, events which would be consequential during viral infection or IFN-driven autoimmune disease.