Panel A contains multiple scatter plots showing the frequencies and absolute counts of natural killer cells, gamma delta T cells, mucosal-associated invariant T cells, and memory cluster of differentiation 4-positive T-helper cells, including T-helper 1, T-helper 2, T-helper 17, and T-helper 1 star subsets, in healthy adult and pediatric controls and in patients with different interleukin-23 receptor genotypes. The horizontal axis represents the different study groups, and the vertical axis represents either the percentage or the absolute number of cells. Panel B contains multiple scatter plots showing the frequencies of cluster of differentiation 4-positive T cells, cluster of differentiation 8-positive T cells, monocytes, and dendritic cells in healthy controls and patients with different interleukin-23 receptor genotypes. The horizontal axis represents the different study groups, and the vertical axis represents the percentage of cells. Panel C contains multiple scatter plots showing the absolute counts of cluster of differentiation 4-positive T cells, cluster of differentiation 8-positive T cells, natural killer cell subsets, monocytes, and dendritic cells in healthy controls and patients with different interleukin-23 receptor genotypes. The horizontal axis represents the different study groups, and the vertical axis represents the number of cells per cubic millimeter. Panel D contains multiple scatter plots showing the frequencies of memory cluster of differentiation 4-positive T-helper cells, including T-helper 1, T-helper 2, T-helper 17, and T-helper 1 star subsets, as well as the absolute counts of natural killer cells, T cells, cluster of differentiation 4-positive T cells, cluster of differentiation 8-positive T cells, natural killer cell subsets, monocytes, and dendritic cells in healthy controls and patients with different interleukin-23 receptor genotypes. The horizontal axis represents the different study groups, and the vertical axis represents either the percentage or the absolute number of cells.
Normal leukocyte development in patients homozygous for hypomorphic IL23R variants. (A) Frequencies and absolute counts of NK, γδ T, and MAIT cells, and frequency of TH1, TH2, TH17, and TH1* memory CD4+ T cells, in healthy adult (n = 35) and pediatric (n = 11) controls, IL23RG149R/G149R (n = 1), IL23RG300V/G300V (n = 1), IL23RR381Q/R381Q (pediatric patients <18 years old [n = 6] and adults >18 years old [n = 3]), and IL23R−/− (n = 2) individuals. (B) Frequencies of CD4+, CD8+, monocytes, and dendritic cells in healthy adults (n = 35) and pediatric (n = 11) controls, adult (n = 3), and pediatric (n = 6) homozygotes for R381Q, an adult homozygous for G149R, and an adult homozygous for G300V IL-23R-deficient patients, as assessed by spectral flow cytometry on fresh PBMCs. The statistical significance of differences was assessed in unpaired Mann–Whitney U tests with *P < 0.05, **P < 0.01. (C) Absolute counts of CD4+, CD8+, and NK subsets; monocytes, and dendritic cells (DCs) in healthy adults (n = 35) and pediatric (n = 11) controls, adult (n = 3) and pediatric (n = 6) patients homozygous for R381Q, one adult homozygous for G300V, and an adult homozygous for G149R IL-23R–deficient patients, assessed by CyTOF cytometry on fresh PBMCs. (D) Frequencies of TH1, TH2, TH17, and TH1* memory CD4+ T cells and absolute counts of NK, γδ T cells, CD4+, CD8+, and NK subset; monocytes, and dendritic cells (DCs) in healthy adults (n = 19) and pediatric (n = 20) controls, IL23RG300V/G300V (n = 1), IL23RR381Q/R381Q (pediatric patients <18 years old [n = 2] and adults >18 years old [n = 1]), IL23R−/− (n = 3) and IL12RB1−/− (n = 1) individuals, as determined with a spectral flow panel not recognizing MAIT cells.