Fig. 3

Genes that are associated with PD-1 signaling are downregulated in inflammatory arthritis. The schematic of the data analysis pipeline shows the transition from the investigation of bulk RNA sequencing data to single-cell RNA sequencing data of patients with inflammatory arthritis (A). Heatmap showing RNA expression levels of top genes of bulk RNA sequencing datasets of RA patients sorted based on highest TIDE scoring (B). Highlighted in the box are downregulated genes, specifically in the T cells of RA patients. Genes in bold letters were also significantly downregulated in subsequent analysis. UMAP plot showing clusters reannotation of single-cell RNA sequencing data of RA patients, prioritizing the genes emphasized in B (C). Cells were clustered based on the T cell subset and by anatomical origin: PB, SF, or synovial tissue (ST). UMAP plots comparing the distribution of two clusters of activated CD8 T cells, CD8 HLA-DRB1⁺ and CD8 CD69⁺, isolated from either PB or SF (D). The expression of genes significantly differentially expressed in the two subsets of activated CD8 T cells is PB compared to SF. UMAP plots comparing the distribution of effector CD4 T cells (CD4 PRF1⁺) to effector CD T cells (CD4 PRF1.⁺) (E). Expression of genes significantly differentially expressed between the CD4 PRF1 + and the CD8 PRF1 + effector subset in the PB and SF compartments. UMAP plots showing cell subsets expressing high levels of KLRG1, CRTAM, SLAMF7, PTPN2, and KLRD1 (F)