Type I interferon signaling attenuates Regulatory T cells function in LCMV infection. Mus musculus

Regulatory T cells (Tregs) play a cardinal role in the immune system by suppressing detrimental autoimmune responses, but their role in acute and chronic infectious diseases remains unclear. We recently demonstrated that IFN- receptor (IFNAR) signaling promotes Treg function in autoimmunity. To dissect the functional role of IFNAR-signaling in Tregs during acute and chronic viral infection, we infected Treg-specific IFNAR deficient (IFNARfl/flxFoxp3YFP-Cre) mice with LCMV Armstrong and Clone-13. In both models, IFNARfl/flxFoxp3YFP-Cre mice Tregs expressed enhanced expression of Treg associated activation antigens. The enhanced activated phenotype was also seen when we compared the transcriptomes of IFNARfl/flxFoxp3YFP-Cre and wild type (WT) Tregs by RNA-Seq on day 25-post Clone-13 infection. LCMV-specific CD8+ T cells from IFNARfl/flxFoxp3YFP-Cre mice produced less antiviral IFN and TNF in both acute and chronic LCMV. In the chronic model, the numbers of anti-viral effector and memory CD8+ T cells were decreased in IFNARfl/flxFoxp3YFP-Cre mice and the effector CD4+ and CD8+ T cells exhibited a phenotype compatible with enhanced exhaustion. IFNARfl/flxFoxp3YFP-Cre mice cleared Armstrong infection normally, but had higher viral titers in sera, kidneys and lungs than WT mice during chronic infection. Thus, type I IFN signaling in Tregs is context-dependent, resulting in enhanced suppressor function in some models of autoimmunity, but decreased suppressor function in acute and chronic viral infection. Overall design: mRNA from Treg cells from 5 WT and 5 IFNAR deficient mice were analyzied by RNA-seq using Illumina HiSeq