Sex Differences in Plasmacytoid Dendritic Cell Levels of IRF5 Drive Higher IFN-α Production in Women.
Morgane GriesbeckSusanne ZieglerSophie LaffontNikaïa SmithLise ChauveauPhillip TomezskoArmon ShareiGeorgio KourjianFilippos PorichisMeghan HartChristine D PalmerMichael SirignanoClaudia BeiselHeike HildebrandtClaire CénacAlexandra-Chloé VillaniThomas J DiefenbachSylvie Le GallOlivier SchwartzJean-Philippe HerbeuvalBrigitte AutranJean-Charles GuéryJ Judy ChangMarcus AltfeldPublished in: Journal of immunology (Baltimore, Md. : 1950) (2015)
Increased IFN-α production contributes to the pathogenesis of infectious and autoimmune diseases. Plasmacytoid dendritic cells (pDCs) from females produce more IFN-α 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-α-secreting pDCs. Delivery of recombinant IRF5 protein into human primary pDCs increased TLR7-mediated IFN-α 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-α 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-α production upon TLR7 stimulation in females and provide novel targets for the modulation of immune responses and inflammation.
Keyphrases
- dendritic cells
- immune response
- estrogen receptor
- regulatory t cells
- toll like receptor
- endothelial cells
- inflammatory response
- transcription factor
- gene expression
- oxidative stress
- type diabetes
- machine learning
- adipose tissue
- atrial fibrillation
- copy number
- single cell
- long non coding rna
- pluripotent stem cells
- polycystic ovary syndrome
- amino acid