Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2018) 54 P4 | DOI: 10.1530/endoabs.54.P4

NuclearReceptors2018 Poster Presentations (1) (7 abstracts)

Selective disruption of ERα expression in dendritic cells of lupus prone mice results in female-specific reduced survival

Melissa A Cunningham 1 , Jena R Wirth 1 , Jackie Eudaly 1 & Gary S Gilkeson 1,


1Medical University of South Carolina, Charleston, South Carolina, USA; 2Ralph H. Johnson Veterans Affairs Hospital, Charleston, South Carolina, USA.


Systemic lupus erythematosus (SLE) is a disease that disproportionately affects females. We previously showed that a functional knockout of estrogen receptor alpha (ERαKO) resulted in significantly reduced renal disease and increased survival in murine lupus. The mechanism of this effect, which requires estrogen, is not known. Interestingly, an ERα−/− (null mutant) mouse is not similarly protected. We and others have demonstrated a role for ERα in dendritic cell (DC) development and Toll-like receptor (TLR) responsiveness. Here we show that selective genetic disruption of ERα in DCs of lupus prone mice results in a survival difference, but unexpectedly only in females, who die prematurely compared with intact females. Floxed-ERα and Cre-CD11c strains were backcrossed onto the NZM2410 lupus-prone background for 12 generations. Males and females were studied (n=24). There was no significant difference in survival between NZM CrePos/Floxed-ERα (DC-specific ERαKO) mice and NZM CreNeg/Floxed-ERα mice. Considered separately, however, female survival was significantly different. Median age at death was 30.0 weeks (±1.8) for the CrePos and 40.4 weeks (±3.9) for the CreNeg females (P<0.04). Spleen cells were isolated and flow cytometry was performed to determine number and subset of DCs. Preliminary flow cytometry results revealed a significantly reduced percent of MHCII+F480-CD11c+CD11b+ DCs and MHCII+B220+SiglecH+ pDCs in CrePos vs. CreNeg mice. There was a trend towards increased percent of MHCII+CD11c+CD11b-CD8a+ cells in CrePos mice. In summary, while selective deletion of ERα in DCs of female lupus-prone mice results in female-specific reduced survival, the etiology of this unexpected accelerated disease phenotype is not clear. This data joins a growing body of evidence that ERα plays an important role in modulating immune cell function.

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Nuclear Receptors: New Roles for Nuclear Receptors in Development, Health and Disease Conference 2018

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