Type I interferon signaling attenuates regulatory T cell function in viral infection and in the tumor microenvironment
Fig 6
Transcriptome analysis of Foxp3+ Tregs from LCMV infected Treg-specific IFNAR-deficient mice.
(A) PCA was performed on day 5 LCMV Armstrong infected Foxp3YFP-Cre and IFNARfl/fl x Foxp3YFP-Cre mice sorted CD4+YFP+ Treg cells RNA-seq samples (4 samples in each group). (B) Scatter plot showing the comparison of global gene expression profiles of Tregs between Armstrong infected Foxp3YFP-Cre and IFNARfl/fl x Foxp3YFP-Cre mice. Total of 586 genes were significantly differentially expressed and colored, 249 genes (red) were down regulated, and 337 genes (blue) upregulated in IFNARfl/fl x Foxp3YFP-Cre mice (fold change 1.5 and above, adjusted P < 0.05). (C) GSEA for non-IFN related genes, showing enrichment plot for natural Treg vs. T conv DN gene set (36 out 42 genes were enriched in core, Enrichment score: 0.566, P < 0.01, FDR: 0.0) with positive enrichment in IFNARfl/fl x Foxp3YFP-Cre mice Tregs relative to Foxp3YFP-Cre mice Tregs. (D) Heat map showing the significant differential expression of 32 Treg-signature genes (fold change 1.5 and above, adjusted P < 0.05), as previously reported [49, 50], differentially expressed genes were normalized by z-score. (E) PCA was performed on day 25 LCMV Cl-13 infected Foxp3YFP-Cre and IFNARfl/fl x Foxp3YFP-Cre mice sorted CD4+YFP+ Treg cells RNA-seq samples (5 samples in each group). (F) Scatter plot showing the comparison of global gene expression profiles of Tregs between Cl-13 infected Foxp3YFP-Cre and IFNARfl/fl x Foxp3YFP-Cre mice. Total of 36 genes were significantly differentially expressed and colored, 23 genes (red) were down regulated, and 13 genes (blue) upregulated in IFNARfl/fl x Foxp3YFP-Cre mice (fold change 1.5 and above, adjusted P < 0.05). (G) Heat map showing the significant differential expression of 22 non-IFN related genes (fold change 1.5 and above, adjusted P < 0.05, normalized by z-score). (H) Heat map showing the significant differential expression of 14 genes from LCMV Armstrong infected Foxp3YFP-Cre mice and IFNARfl/fl x Foxp3YFP-Cre mice Tregs, which were in consistent with transcriptome from LCMV Cl-13 infected mice Tregs (fold change 1.5 and above, adjusted P < 0.05, normalized by z-score). Armstrong infection transcriptome data obtained from an experiment involving four mice per group (A-D and H), and transcriptome data from Cl-13 infection, involved an experiment with five mice per group (E-G).