The long noncoding RNA Morrbid regulates CD8 T cells in response to viral infection.

Document Type

Article

Publication Date

6-11-2019

Keywords

JGM

JAX Source

Proc Natl Acad Sci U S A 2019 Jun 11; 116(24):11916-925

Volume

116

Issue

24

First Page

11916

Last Page

11925

ISSN

1091-6490

PMID

31138702

DOI

https://doi.org/10.1073/pnas.1819457116

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.

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