(A) Heatmaps reflecting log₂FC in transcription of 42 genes associated with Fc-receptor signaling on sorted Mo, CD1c⁺, and CD141⁺ cDC from the peripheral blood (PB) of n = 4 RA individuals compared with corresponding n = 4 healthy controls (HC). Significant DEG are highlighted in yellow (left heatmap, FDR-corrected P < 0.05) dots. Size of yellow dots is proportional to significance level. (B) qPCR analysis of expression of IL-1β (n = 6), IL-8, and CCL3 (n = 7) relative to β-actin in circulating cDC cultured for 24 hours in the presence of media or human IgG (hIgG) complexes alone (yellow bars) or in combination with dsDNA (pink bars) or media containing dsDNA (purple bars). *P < 0.05; **P < 0.01. (C) Proportions of CD40⁺CD86^hi cDC (left) and mean fluorescence intensity (MFI) of CD40 on these cells (right) and analyzed by FACS in the experiments detailed in B. *P < 0.05; **P < 0.01. (D) ELISA quantification of IL-1β on culture supernatants of CD1c⁺ cDC exposed to media or hIgG-dsDNA complexes for 24 hours. Significance was calculated using a 2-tailed Wilcoxon pairs-matched test. *P < 0.05. (E) Representative confocal microscopy image (magnification, 40×/1.4-0.75) analyzing expression of Caspase 1, CD1c, and HLA-DR on histological sections from inflamed synovial membrane from a representative RA patient from n = 3 individuals tested. (F) Proportions of CD40^hiCD86^hi cDC cultured in media alone or activated with Ig-dsDNA complexes in the presence or either DMSO, a Caspase 1/NF-κB inhibitor, or a NLRP3 inhibitor (n = 8 experiments). Statistical significance was calculated using a 2-tailed Wilcoxon test. *P < 0.05; **P < 0.01.