Estrogen receptor alpha modulates toll-like receptor signaling in murine lupus
- 作者：Melissa A. Cunningham ; Osama S. Naga ; Jackie G. Eudaly ; Jennifer L. Scott ; Gary S. Gilkeson ; gilkeson@musc.edu
- 关键词：Estrogen receptor alpha ; Systemic lupus erythematosus ; Dendritic cells ; Toll-like receptors
- 刊名：Clinical Immunology
- 出版年：2012
- 期刊代码：95_15216616
- 类别：imm
- 出版时间：July, 2012
- 卷：144
- 期：1
- 页码：1-12
- 文件大小：1213 K
摘要
Systemic lupus erythematosus (SLE) is a disease that disproportionately affects females. Despite significant research effort, the mechanisms underlying the female predominance in this disease are largely unknown. Previously, we showed that estrogen receptor alpha knockout (ER伪KO) lupus prone female mice had significantly less pathologic renal disease and proteinuria, and significantly prolonged survival. Since autoantibody levels and number and percentage of B/T cells were not significantly impacted by ER伪 genotype, we hypothesized that the primary benefit of ER伪 deficiency in lupus nephritis was via modulation of the innate immune response. Using BMDCs and spleen cells/B cells from female wild-type or ER伪KO mice, we found that ER伪KO-derived cells have a significantly reduced inflammatory response after stimulation with TLR agonists. Our results indicate that the inflammatory response to TLR ligands is significantly impacted by the presence of ER伪 despite the absence of estradiol, and may partially explain the protective effect of ER伪 deficiency in lupus-prone animals.