Medical University of South Carolina, Division of Rheumatology and Immunology and Ralph H. Johnson Veterans Affairs Hospital, Charleston, SC 29425, USA.
Clin Immunol. 2012 Jul;144(1):1-12. doi: 10.1016/j.clim.2012.04.001. Epub 2012 Apr 20.
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 (ERαKO) 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 ERα genotype, we hypothesized that the primary benefit of ERα deficiency in lupus nephritis was via modulation of the innate immune response. Using BMDCs and spleen cells/B cells from female wild-type or ERαKO mice, we found that ERαKO-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 ERα despite the absence of estradiol, and may partially explain the protective effect of ERα deficiency in lupus-prone animals.
系统性红斑狼疮（SLE）是一种女性发病率明显偏高的疾病。尽管进行了大量研究，但该病女性高发的机制在很大程度上仍不清楚。先前我们发现，雌激素受体α 敲除（ERαKO）狼疮易感雌性小鼠的肾脏病理疾病和蛋白尿明显减少，且生存时间明显延长。由于自身抗体水平以及 B/T 细胞的数量和比例不受 ERα 基因型的显著影响，我们假设 ERα 缺乏在狼疮肾炎中的主要益处是通过调节固有免疫反应。使用 BMDCs 和来自雌性野生型或 ERαKO 小鼠的脾细胞/B 细胞，我们发现 ERαKO 衍生的细胞在受到 TLR 激动剂刺激后炎症反应明显减弱。我们的结果表明，尽管缺乏雌二醇，但 TLR 配体的炎症反应受到 ERα 的显著影响，这可能部分解释了 ERα 缺乏在狼疮易感动物中的保护作用。
