The long noncoding RNA Morrbid regulates CD8 T cells in response to viral infection.
Jonathan J KotzinFany IsekaJasmine WrightMegha G BasavappaMegan L ClarkMohammed-Alkhatim AliMohamed S Abdel HakeemTanner F RobertsonWalter K MowelLeonel JoannasVanessa D NealSean P SpencerCamille M SyrettMontserrat C AngueraAdam WilliamsE John WherryJorge Henao-MejiaPublished in: Proceedings of the National Academy of Sciences of the United States of America (2019)
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.
Keyphrases
- long noncoding rna
- signaling pathway
- dendritic cells
- genome wide association study
- transcription factor
- sars cov
- public health
- regulatory t cells
- genome wide
- immune response
- poor prognosis
- papillary thyroid
- drug induced
- liver failure
- long non coding rna
- multidrug resistant
- gene expression
- pi k akt
- genome wide association
- gram negative
- squamous cell
- oxidative stress
- binding protein
- induced apoptosis
- aortic dissection
- drug delivery
- squamous cell carcinoma
- free survival
- extracorporeal membrane oxygenation
- network analysis
- nucleic acid
- genome wide analysis
- childhood cancer
- genome wide identification
- mechanical ventilation