Sex-based differences control the TLR-7-mediated response of human pDCs in vivo. (A-B) pDCs derived from premenopausal women (18-45 years old, n = 20) or age-matched male donors (n = 15) were stimulated with TLR-7/TLR-8 ligand R-848 and stained for IFN-α and TNF-α. Percentage of IFN-α (A) and TNF-α (B) positive pDCs in premenopausal women (18-45 years old, n = 20) compared with men (n = 15). (C-E) Female or male NOD/SCID/β2m^−/− were sublethally irradiated and transplanted with human CD34⁺ hematopoietic progenitor cells from 3 different female donors. (C) After 8 weeks, human pDCs were identified as the CD45⁺ CD123⁺ BDCA-4⁺ compartment in bone marrow cells. (D-E) Bone marrow cells were restimulated ex vivo as in panel A. The frequencies of IFN-α (D) and TNF-α (E) producing pDCs were determined by flow cytometry. Horizontal lines in scatter plots on the right panels indicate mean values. Statistical difference between groups was assessed using the Mann-Whitney U test.