Pencovich Niv, Luk Janelle, Hantisteanu Shay, Hornstein Mark D, Fainaru Ofer
Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel.
Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA 02115, USA; Vascular Biology Program, Department of Surgery, Children's Hospital Boston, both at Harvard Medical School, Boston, MA 02115, USA.
Reprod Biomed Online. 2014 Apr;28(4):515-21. doi: 10.1016/j.rbmo.2013.12.011. Epub 2014 Jan 17.
Endometriosis is a common condition associated with pelvic pain and infertility. This study group has previously shown that supplementation of dendritic cells led to enhancement of endometriosis lesion growth and angiogenesis. This study determined whether endometriosis is dependent on the presence of endogenous dendritic cells. Surgical induction of endometriosis was performed in CD11c⁺ DTR/GFP transgenic (Tg) female mice in which dendritic cells were ablated upon injection of diphtheria toxin (DT). Mice were allocated into four groups (n=5 each): group I, wild-type mice treated with vehicle; group II, wild-type mice treated with DT; group III, Tg mice treated with DT; and group IV, Tg mice treated with vehicle. After 10 days, mice were killed and endometriosis lesions were analysed by flow cytometry. DT treatment led to ablation of dendritic cells in spleens and endometriosis lesions in Tg mice while no ablation was observed in controls. Corresponding to dendritic cell ablation, endometriosis lesions in group III were ∼5-fold smaller than in the control groups (ANOVA P<0.0001). This study suggests that endometriosis development is dependent on the presence of endogenous dendritic cells. Therapies designed to inhibit dendritic cell infiltration as possible treatments for endometriosis warrant further study.
子宫内膜异位症是一种与盆腔疼痛和不孕相关的常见病症。该研究小组先前已表明,补充树突状细胞会导致子宫内膜异位症病灶生长和血管生成增强。本研究确定子宫内膜异位症是否依赖内源性树突状细胞的存在。在CD11c⁺ DTR/GFP转基因(Tg)雌性小鼠中进行子宫内膜异位症的手术诱导,在这些小鼠中,注射白喉毒素(DT)后树突状细胞会被清除。将小鼠分为四组(每组n = 5):第一组,用赋形剂处理的野生型小鼠;第二组,用DT处理的野生型小鼠;第三组,用DT处理的Tg小鼠;第四组,用赋形剂处理的Tg小鼠。10天后,处死小鼠并通过流式细胞术分析子宫内膜异位症病灶。DT处理导致Tg小鼠脾脏中的树突状细胞和子宫内膜异位症病灶被清除,而对照组未观察到清除现象。与树突状细胞清除相对应,第三组的子宫内膜异位症病灶比对照组小约5倍(方差分析P < 0.0001)。本研究表明,子宫内膜异位症的发展依赖于内源性树突状细胞的存在。旨在抑制树突状细胞浸润作为子宫内膜异位症可能治疗方法的疗法值得进一步研究。