Sex Differences in Plasmacytoid Dendritic Cell Levels of IRF5 Drive Higher IFN-? Production in Women.

ABSTRACT: Increased IFN-? production contributes to the pathogenesis of infectious and autoimmune diseases. Plasmacytoid dendritic cells (pDCs) from females produce more IFN-? upon TLR7 stimulation than pDCs from males, yet the mechanisms underlying this difference remain unclear. In this article, we show that basal levels of IFN regulatory factor (IRF) 5 in pDCs were significantly higher in females compared with males and positively correlated with the percentage of IFN-?-secreting pDCs. Delivery of recombinant IRF5 protein into human primary pDCs increased TLR7-mediated IFN-? secretion. In mice, genetic ablation of the estrogen receptor 1 (Esr1) gene in the hematopoietic compartment or DC lineage reduced Irf5 mRNA expression in pDCs and IFN-? production. IRF5 mRNA levels furthermore correlated with ESR1 mRNA levels in human pDCs, consistent with IRF5 regulation at the transcriptional level by ESR1. Taken together, these data demonstrate a critical mechanism by which sex differences in basal pDC IRF5 expression lead to higher IFN-? production upon TLR7 stimulation in females and provide novel targets for the modulation of immune responses and inflammation.

SUBMITTER: Griesbeck M 

PROVIDER: S-EPMC4654231 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature