Maridas David E, Hey-Cunningham Alison J, Ng Cecilia H M, Markham Robert, Fraser Ian S, Berbic Marina
Department of Obstetrics, Gynaecology and Neonatology, Queen Elizabeth II Research Institute for Mothers and Infants, The University of Sydney, Sydney - Australia.
J Endometr Pelvic Pain Disord. 2014 Apr-Jun;6(2):67-119. doi: 10.5301/je.5000180. Epub 2014 Jun 30.
Dysfunctional immune response may be implicated in endometriosis pathogenesis, and dendritic cells (DC) may play greater roles in this response than previously recognized. This study set out to evaluate peripheral blood and endometrial DC population changes in the presence and absence of endometriosis pathology.
Endometrial (n = 83) and peripheral blood samples (n = 30) were subjected to immunohistochemical techniques and flow cytometry, respectively, to assess DC populations in women with and without endometriosis. Three circulating DC subsets (MDC1, MDC2 and PDC, expressing CD1c, CD303 and CD141), and late-stage mature endometrial DCs (using DC-LAMP antibody) were investigated.
A highly significant reduction in CD1c intensity on MDC1 populations in peripheral blood was observed between normal cycle proliferative and menstrual phases (p = 0.025), but not in women with endometriosis, in whom CD1c intensity was markedly increased at the time of menstruation (p = 0.05). A significant reduction in peripheral blood MDC2 (p = 0.016) and apparent reduction in endometrial DC-LAMP+ DC (trend, p = 0.062) were observed in women with endometriosis compared with controls, consistent with our preliminary DC data.
Cyclical variation in endometrial and circulating DC populations appears to be crucial during normal menstrual cycles and in the establishment of pregnancy. In endometriosis, circulating and endometrial DC populations are significantly dysregulated at a number of levels, and are likely to contribute to inefficient immunological targeting of endometrial fragments shed at menstruation, facilitating their survival and establishment of endometriosis.
功能失调的免疫反应可能与子宫内膜异位症的发病机制有关,并且树突状细胞(DC)在这种反应中可能发挥比以往认识到的更大作用。本研究旨在评估存在和不存在子宫内膜异位症病理情况下外周血和子宫内膜DC群体的变化。
分别对83例子宫内膜样本和30例外周血样本进行免疫组织化学技术和流式细胞术,以评估有和没有子宫内膜异位症的女性的DC群体。研究了三种循环DC亚群(MDC1、MDC2和PDC,分别表达CD1c、CD303和CD141)以及晚期成熟子宫内膜DC(使用DC-LAMP抗体)。
在正常周期的增殖期和月经期之间,观察到外周血中MDC1群体上CD1c强度显著降低(p = 0.025),但子宫内膜异位症患者中未出现这种情况,在这些患者中,月经期时CD1c强度显著增加(p = 0.05)。与对照组相比,子宫内膜异位症患者外周血MDC2显著减少(p = 0.016),子宫内膜DC-LAMP+ DC明显减少(趋势,p = 0.062),这与我们初步的DC数据一致。
子宫内膜和循环DC群体的周期性变化在正常月经周期和妊娠建立过程中似乎至关重要。在子宫内膜异位症中,循环和子宫内膜DC群体在多个水平上显著失调,并且可能导致月经期间脱落的子宫内膜碎片免疫靶向效率低下,促进它们的存活和子宫内膜异位症的形成。