Female lupus-prone NZM2410 estrogen receptor á (ERá)-deficient mice are protected from renal disease and have prolonged survival compared with wild-type littermates; however, the mechanism of protection is unknown. Plasmacytoid dendritic cells (pDCs) and type I IFN drive lupus pathogenesis. Estrogen acting via ERá enhances both pDC development and IFN production. The objectives for this study were to determine if ERá modulates pDC function and IFN activity in predisease NZM2410 mice as a possible protective mechanism of ERá deficiency in lupus-prone mice. We measured the effect of ERá deficiency on spleen pDC frequency, number, maturation, and activation state. ERá deficiency reduced type I IFN activity and the frequency of MHC class II(+) pDCs in the spleen without altering overall pDC frequency, number, or maturation state. Additionally, ERá-deficient NZM2410 mice had a significantly decreased frequency of pDCs expressing PDC-TREM, a modulator of TLR-mediated IFN production. After in vitro TLR9 stimulation, ERá deficiency significantly reduced the expression of PDC-TREM on pDCs from both NZM2410 and C57BL/6 mice. Thus, we have identified a significant effect of ERá deficiency on pDCs in predisease NZM2410 mice, which may represent a mechanism by which ERá deficiency protects NZM2410 mice from lupuslike disease.
Animals Cells, Cultured