MiR31 increases CD8 T cell sensitivity to type I interferon

We report that the microRNA (miR)-31 confers CD8 T cell sensitivity to type I interferon (IFN) stimulation following CD3/CD28 engagement. Method: miR31 WT and KO CD8 T cells were stimulated with anti-CD3/CD28 beads for two days, then maintained in 10ng/mL IL-2 for a further 5 days. CD8 T cells were then stimulated with 20ng/mL IFN-beta for 0, 4, or 18h. Total RNA was isolated at each time point and sequenced. Results: Prior to IFN-beta stimulation, miR-31 KO CD8 T cells had a slightly increased effector program (cytotoxic granzymes) and decreased inhibitory program (Mt1/Maf). Stimulation with IFN-beta further enhanced this difference increasing a number of granzymes, Prf1 and Spp1 whilst also decreasing inhibitory genes (Mt1, Mt2, Maf, Ptger2). Conclusion: This study shows that miR-31 may lead to decreased effector function and increased inhibitory programs in CD8 T cells during chronic viral infections, in particular due to continued type I interferon stimulation. RNA profiles of miR31 WT or KO CD8 T cells were generated in triplicate following a 7 day TCR/IL-2 stimulation followed by 0, 4, or 18 hours IFN-beta stimulation.