Sbracia Marco, McKinnon Brett, Scarpellini Fabio, Marconi Daniela, Rossi Gabriele, Simmilion Cedric, Mueller Michael D, Barnea Eytan R, Mueller Martin
Hungaria Center for Endocrinology and Reproductive Medicine, Rome, Italy.
Department of Clinical Research, University of Bern, Bern, Switzerland.
PLoS One. 2017 Sep 13;12(9):e0184399. doi: 10.1371/journal.pone.0184399. eCollection 2017.
Endometriosis is a chronic inflammatory condition characterised by the growth of endometrial epithelial and stromal cells outside the uterine cavity. In addition to Sampson's theory of retrograde menstruation, endometriosis pathogenesis is facilitated by a privileged inflammatory microenvironment, with T regulatory FoxP3+ expressing T cells (Tregs) being a significant factor. PreImplantation Factor (PIF) is a peptide essential for pregnancy recognition and development. An immune modulatory function of the synthetic PIF analog (sPIF) has been successfully confirmed in multiple animal models. We report that PIF is expressed in the epithelial ectopic cells in close proximity to FoxP3+ stromal cells. We provide evidence that PIF interacts with FoxP3+ cells and modulates cell viability, dependent on cell source and presence of inflammatory mediators. Our finding represent a novel PIF-based mechanism in endometriosis that has potential for novel therapeutics.
子宫内膜异位症是一种慢性炎症性疾病，其特征是子宫内膜上皮细胞和间质细胞在子宫腔外生长。除了桑普森的逆行月经理论外，子宫内膜异位症的发病机制还受到特殊炎症微环境的促进，表达调节性T细胞FoxP3+的T细胞（Tregs）是一个重要因素。着床前因子（PIF）是妊娠识别和发育所必需的一种肽。合成PIF类似物（sPIF）的免疫调节功能已在多个动物模型中得到成功证实。我们报告PIF在与FoxP3+间质细胞紧邻的上皮异位细胞中表达。我们提供的证据表明，PIF与FoxP3+细胞相互作用并调节细胞活力，这取决于细胞来源和炎症介质的存在。我们的发现代表了子宫内膜异位症中一种基于PIF的新机制，具有开发新型治疗方法的潜力。
