Fig. 2: Diversion of Tc17 cells towards a “CTL-like” genetic signature upon DMF treatment. | Nature Communications

Fig. 2: Diversion of Tc17 cells towards a “CTL-like” genetic signature upon DMF treatment.

From: IL-17+ CD8+ T cell suppression by dimethyl fumarate associates with clinical response in multiple sclerosis

Fig. 2

a RNA-Seq based heatmap of 281 differentially expressed (DE) genes (p adjusted [p adj] < 0.01 and log2FC ≥ 0.75) between Ctrl ± DMF or DMF + GSH-treated murine Tc17 cells differentiated for 48 h (n = 3). Highlighted are genes associated with type 17 or CTL signature. b Expression-ratio of Rorc-to-Tbx21 calculated from RNA-Seq from a, normalized to the DMF values, which were arbitrarily set to 1. c Flow cytometry of RORγt or T-BET in murine Tc17 cells differentiated for 72 h, to the right, ratio of RORγt-to-T-BET calculated from fold MFI. d, e GSEA of genes associated with Tc17 d or CTL e phenotype as defined by GSE110346 in Tc17 cells from a. f Venn diagram of DMF-dependent DE genes in murine Tc17 (dataset from a) and human CD8+CD45RA− T cells from matched groups of MS patients “DMF untreated” (n = 4) and “DMF treated” (n = 4), who fulfilled NEDA-3 criteria after 12–13 months of DMF therapy (Supplementary Table 4 and Supplementary Fig. 2b) based on RNA-Seq (p adj < 0.1). g Scatter plot of overlapping gene regulation in murine Tc17 and human CD8+CD45RA− T cells datasets from a and f, respectively (p adj < 0.1). Highlighted are concordantly expressed genes associated with Tc17 or CTL phenotype. h Heatmap of top transcripts with correlating expression in murine Tc17 and human CD8+CD45RA− T cell-datasets from a, f, respectively. DE mouse Tc17 transcripts (p adj < 0.01, log2Fc ≥ 0.6), and corresponding 182 human transcripts with GSEA core enrichment were selected. Highlighted are genes associated with Tc17 and CTL phenotype. i Relative expression of RORC-to-TBX21 calculated from RNA-seq from f. j GSEA of genes associated with ROS-signaling in human CD8+CD45RA− T cells from f based on MSigDBv6.1. k, l GSEA of genes associated with IL17+CD8+ k or IL17−CD8+ l profiles in CD8+CD45RA− T cells from f based on published raw data (RNA-Seq GSE96741)42. Bars show mean ± s.d. from four to three b, c, i combined experiments; individual values are plotted. In b, c *p < 0.05, ***p < 0.001 evaluated by one-way ANOVA followed by Tukey’s HSD multiple comparison test, in i p-value by the two-tailed, unpaired t-test.

Back to article page