| Literature DB >> 31138702 |
Jonathan J Kotzin1,2, Fany Iseka1,2, Jasmine Wright1,2, Megha G Basavappa1,2,3, Megan L Clark1,2, Mohammed-Alkhatim Ali2,4,5, Mohamed S Abdel-Hakeem2,4,6, Tanner F Robertson1, Walter K Mowel1,2, Leonel Joannas1,2, Vanessa D Neal1,2, Sean P Spencer1,2, Camille M Syrett2,7, Montserrat C Anguera2,7, Adam Williams8,9, E John Wherry2,4,5, Jorge Henao-Mejia10,2,11.
Abstract
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.Entities:
Keywords: CD8 T cells; lncRNAs; viral infection
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Year: 2019 PMID： 31138702 PMCID： PMC6575676 DOI： 10.1073/pnas.1819457116
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205