Panel A: Two UMAP plots show the clustering of PBMCs based on group and predicted cell type. The left plot is color-coded by different groups, including controls and various genetic conditions. The right plot is color-coded by predicted cell types, such as CD4 T cells, NK cells, and MAIT cells. Panel B: A scatter plot displays the percentage of different leukocyte subsets in PBMCs from various groups, including controls and patients with different genetic conditions. Each subset is represented by a different symbol and color. Panel C: Two scatter plots show the relative abundance of leukocyte subsets at steady state (left) and after IL-23 stimulation (right). The plots are color-coded by different groups, including controls and patients with various genetic conditions. Panel D: Four two-dimensional plots show the fold-change difference in IFNG mRNA levels following IL-23 stimulation in leukocytes from different patient groups relative to controls. The x-axis represents the fold-change difference for IL23RR381Q/R381Q, IL23RG300V/G300V, IL23RG149R/G149R, and TYK2P1104A/P1104A patients, while the y-axis represents the same parameter for IL-12R1 knockout patients. The color of the circles indicates the median change in normalized IFNG mRNA levels in controls for the corresponding subsets, with MAIT, NK, and V2 positive T cells highlighted.
Single-cell sequencing analysis of PBMCs from IL-23R–deficient patients. (A) UMAP representation of scRNAseq performed on PBMCs from 11 healthy controls, 3 IL23RR381Q/R381Q, 2 IL23RG300V/G300V, 1 IL23RG149R/G149R, 3 IL23R−/−, 3 IL12Rβ1−/−, and 3 TYK2P1104A/P1104A patients. (B) Proportions of leukocyte subsets from the individuals in A at steady state. (C) Relative abundance of each leukocyte subset according to clustering analysis for non-stimulated and IL-23–stimulated samples. (D) Two-dimensional plots of IL-23–induced delta IFNG expression. The fold-change difference in IFNG mRNA levels following IL-23 stimulation in leukocytes from IL23RR381Q/R381Q, IL23RG300V/G300V, IL23RG149R/G149R, and TYK2P1104A/P1104A patients relative to controls is shown on the x-axis. The y-axis shows the same parameter for IL-12Rβ1−/− patients as a comparison. The color of the circles indicates the median change (IL-23 versus NS) in normalized IFNG mRNA levels in controls for the corresponding subsets. MAIT, NK, and Vδ2+ γδT cells are highlighted.