The long noncoding 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 noncoding RNAs (lncRNAs) and the loci that transcribe them contribute to the regulation of CD8 T cells during...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2019-06, Vol.116 (24), p.11916-11925
Main Authors: Kotzin, Jonathan J., Iseka, Fany, Wright, Jasmine, Basavappa, Megha G., Clark, Megan L., Ali, Mohammed-Alkhatim, 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, Henao-Mejia, Jorge
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
AKT protein
Animals
Apoptosis
Biological Sciences
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - virology
Cell differentiation
Cell Differentiation - immunology
Cell survival
Chronic infection
Differentiation (biology)
Immunosurveillance
Inflammation
Interferon
Interferon Type I - immunology
Loci
Lymphocyte Activation - immunology
Lymphocytes
Lymphocytes T
Lymphocytic Choriomeningitis - immunology
Lymphocytic Choriomeningitis - virology
Lymphocytic choriomeningitis virus - immunology
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Phosphatidylinositol 3-Kinases - immunology
PNAS Plus
Proto-Oncogene Proteins c-bcl-2 - immunology
Receptors, Antigen, T-Cell - immunology
Ribonucleic acid
RNA
RNA, Long Noncoding - immunology
Signal transduction
Signal Transduction - immunology
T cell receptors
Transcription
Viral infections
Viruses
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Description
Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1819457116