The long noncoding RNA Morrbid regulates CD8 T cells in response to viral infection.
Proc Natl Acad Sci U S A 2019 Jun 11; 116(24):11916-925
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 noncoding 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 proapoptotic 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.
Kotzin, Jonathan J; Iseka, Fany; Wright, Jasmine; Basavappa, Megha G; Clark, Megan L; Ali, Mohammed-Alkhatim; Abdel-Hakeem, Mohamed S; Robertson, Tanner F; Mowel, Walter K; Joannas, Leonel; Neal, Vanessa D; Spencer, Sean P; Syrett, Camille M; Anguera, Montserrat C; Williams, Adam; Wherry, E John; and Henao-Mejia, Jorge, "The long noncoding RNA Morrbid regulates CD8 T cells in response to viral infection." (2019). Faculty Research 2019. 144.