Fig 1: Monocytes and Dendritic Cells in the Blood Drive Type I Interferonopathy in Patients with ISG15 Mutations(A) Relative mRNA levels for IFIT1, MX1, RSAD2, IFI44L, and IFI27 in peripheral blood from a healthy control, P1,P2, P3, and P5, as assessed by qRT-qPCR. Bars represent the mean ± SD.(B) PBMCs from patients and healthy controls were immunophenotyped by CyTOF technology with a 40-marker panel. t-Stochastic neighbor embedding (t-SNE) plot of PBMCs from P1 and three healthy controls, showing SIGLEC1 (CD169) expression in the various immune populations. The monocyte compartment displays high levels of SIGLEC1 (CD169) expression in P1.(C) SIGLEC1 (CD169) expression in the various subtypes of monocytes (CD14+CD16-, CD14+CD16+, and CD14-CD16+).(D) SIGLEC1 (CD169) expression in dendritic cells.(E) PBMCs from P1 and a control were analyzed by CyTOF. with a panel including several activated signaling markers. Heatmaps show the median expression levels of STAT1 and STAT3 in P1 relative to a healthy control, for the various immune cell subtypes.(F) PBMCs from P1 and a control were analyzed by CyTOF. with a panel including several activated signaling markers. Heatmaps show the median expression levels of pSTAT1, pSTAT3, pSTAT5, pSTAT6, pp38, pMAPKAP2, pERK, and pS6 in P1 relative to a healthy control, for the various immune cell subtypes.