The long non-coding RNA Morrbid regulates CD8 T cells in response to viral infection. The long non-coding RNA Morrbid regulates CD8 T cells in response to viral infection

The transcriptional programs that regulate CD8 T cell differentiation and function in the context of viral infections or tumor immune surveillance have been extensively studied; yet, how long non-coding RNAs (lncRNAs) and the loci that transcribe them contribute to the regulation of CD8 T cells during viral infections remains largely unexplored. Here, we report that transcription of the lncRNA Morrbid is specifically induced by T cell receptor (TCR) and type I IFN stimulation during the early stages of acute and chronic lymphocytic choriomeningitis virus (LCMV) infection. In response to type I IFN, the Morrbid RNA and its locus control CD8 T cell expansion, survival, and effector function by regulating the expression of the pro-apoptotic factor, Bcl2l11, and by modulating the strength of the PI3K-AKT signaling pathway. Thus, our results demonstrate that inflammatory cue-responsive lncRNA loci represent fundamental mechanisms by which CD8 T cells are regulated in response to pathogens and potentially cancer. Overall design: Total RNA profiles of stimulated sorted naïve (CD62Lhi CD44lo) wild type and Morrbid-/- CD8 T cells