X-Chromosome Complement and Estrogen Receptor Signaling Independently Contribute to the Enhanced TLR7-Mediated IFN-α Production of Plasmacytoid Dendritic Cells from Women

摘要: Human plasmacytoid dendritic cells (pDCs) play a major role in innate immunity through the production of type I IFNs after TLR engagement by pathogens. Sex-based differences function human pDCs have been established, with from women exhibiting enhanced TLR7-mediated IFN-α as compared males. In mice, we recently provided evidence for estrogens positive regulator pDC functions cell-intrinsic estrogen receptor α signaling, but did not exclude other X-linked factors, particularly pDCs. this study, investigated respective contribution X chromosome dosage and sex hormones using humanized mouse model which male or female NOD-SCID-β2m(-/-) were transplanted progenitor purified either cord blood cells. We showed that, response to TLR7 ligands, frequency IFN-α- TNF-α-producing was greater than host suggesting estrogens. Indeed, blockade signaling during development vitro inhibited pDCs, expressed both ESR1 ESR2 genes. Interestingly, also found that contributed bias an ones, irrespective recipient mice. Together, these results indicate hormones, estrogens, complement independently contribute women.