Fig. 5: Expansion of IL7R⁺ memory cells in the metabolic active CD4⁺ cells of hyperinsulinemic patients with type 2 diabetes.

A Heatmap of standardized expression sum (SES) of metabolic pathway genes in CD4⁺ T cell clusters of type 2 diabetes (T2D) and healthy controls (HC), by single cell transcriptome. GO-terms used for pathway annotation are Glycolysis (GO:0006096); oxidative phosphorylation (OxPhos, GO:0006119 and GO:0022900); pentose phosphate pathway (PPP, GO:0006098); tricarboxylic acid cycle (TCA, GO:0006099). B Violin plot of insulin signaling (IS) SES of genes INSR, IRS1, IRS2, IGF1R in T cell clusters of T2D and HC. Chi-square test p-value is indicated. C Heatmap of expression for IL7R-signaling targets (C1) and markers of Tph cluster (C2) in IL7R⁺ clusters cells with high and low IS. P-values are calculated by Wilcoxon unpaired test. Asterisks indicate p-values * < 0.05, ** < 0.01, *** <0.001, **** <0.0001. D Violin plot of SES of metabolic pathways (annotated as above) in metabolic active cells with high and low IS of T2D patients. P-values are calculated by Wilcoxon unpaired test. Asterisks indicate p-values * < 0.05, ** < 0.01, *** <0.001, **** <0.0001. E Heatmap of expression difference in metabolic pathways (E1), insulin signaling (E2), IL7R-signaling targets (E3), markers of IL7R⁺ cluster (E4) and Tph clusters (E5) in RNA-seq PBMC of HC orally treated with metformin for 10 h, 7 days. Difference is calculated by Deseq2 analysis and presented by log2 fold change (FC). Asterisks indicate nominal p-values, *<0.05, ** < 0.01, *** < 0.0001. F Heatmap of expression difference in IL7R-signaling targets (F1), markers of IL7R⁺ clusters (F2) and Tph cluster (F3), by RNA-seq of CD4⁺ T cells from RA patients treated with JAKi (25 treated, 9 untreated), abatacept (ABA1, n = 22, paired), methotrexate (MTX, n = 28, paired), tocilizumab (Toci, n = 6, paired). Difference is calculated by Deseq2 analysis and presented by log2FC. Asterisks indicate p-values * < 0.05, ** < 0.01, *** <0.001, **** <0.0001.