Fig. 2

Differential impacts of TNFis on the transcriptome of Th cells. A Th cells were purified from PBMCs pre-stimulated in the presence or absence of 5X ada. The transcript levels of IL-17F and IL-2 were quantified with qPCR. The levels of anti-CD3-stimulated samples were arbitrarily set as 1. B–G Th cells were purified from PBMCs (5 donors) pre-stimulated with anti-CD3/anti-CD28 in the presence or absence of 5X ada (all 5 donors) or cert (donor #4 and #5) and subjected to RNA-seq. A volcano plot of genes whose expression was inhibited or induced by ada in all 5 donors are shown in B. The red dotted lines indicate p ≤ 0.015 and fold change ≥ 1.8 fold. The STRING reactomes of ada-suppressed and ada-induced genes are shown in C and E, respectively. The type 1 IFN-inducible genes identified by Interferome are indicated in E. The effects of ada and cert on the expression of the ada-regulated genes according to the RNA-seq data from donor #4 and #5 are compared in the heatmaps shown in D and F. The fold changes (+drug/-drug ratios) in the transcript levels are shown on the right of the heatmaps. Heatmaps displaying the effect of ada on the expression of the indicated transcription factors (G), Notch pathway, and IL-10 (H) from all 5 donors are also shown