De Leo Bianca, Esnal-Zufiaurre Arantza, Collins Frances, Critchley Hilary O D, Saunders Philippa T K
MRC Centres for Inflammation Research and Reproductive Health, The University of Edinburgh, Edinburgh, EH16 4TJ, UK.
MRC Centre for Inflammation Research, The University of Edinburgh, Edinburgh, EH16 4TJ, UK.
F1000Res. 2017 May 12;6:667. doi: 10.12688/f1000research.11432.2. eCollection 2017.
Human mast cells (MCs) are long-lived tissue-resident immune cells characterised by granules containing the proteases chymase and/or tryptase. Their phenotype is modulated by their tissue microenvironment. The human uterus has an outer muscular layer (the myometrium) surrounding the endometrium, both of which play an important role in supporting a pregnancy. The endometrium is a sex steroid target tissue consisting of epithelial cells (luminal, glandular) surrounded by a multicellular stroma, with the latter containing an extensive vascular compartment as well as fluctuating populations of immune cells that play an important role in regulating tissue function. The role of MCs in the human uterus is poorly understood with little known about their regulation or the impact of steroids on their differentiation status. The current study had two aims: 1) To investigate the spatial and temporal location of uterine MCs and determine their phenotype; 2) To determine whether MCs express receptors for steroids implicated in uterine function, including oestrogen (ERα, ERβ), progesterone (PR) and glucocorticoids (GR). Tissue samples from women (n=46) were used for RNA extraction (n=26) or fixed (n=20) for immunohistochemistry. Messenger RNAs encoded by (tryptase) and (chymase) were detected in endometrial tissue homogenates. Immunohistochemistry revealed the relative abundance of tryptase MCs was myometrium>basal endometrium>functional endometrium. We show for the first time that uterine MCs are predominantly of the classical MC subtypes: (positive, +; negative, -) tryptase+/chymase- and tryptase+/chymase+, but a third subtype was also identified (tryptase-/chymase+). Tryptase+ MCs were of an ERβ+/ERα-/PR-/GR+ phenotype mirroring other uterine immune cell populations, including natural killer cells. Endometrial tissue resident immune MCs have three protease-specific phenotypes. Expression of both ERβ and GR in MCs mirrors that of other immune cells in the endometrium and suggests that MC function may be altered by the local steroid microenvironment.
人类肥大细胞（MCs）是一种寿命较长的驻留组织免疫细胞，其特征是含有蛋白酶类糜蛋白酶和/或类胰蛋白酶的颗粒。它们的表型受其组织微环境调节。人类子宫有一层外层肌肉层（肌层）包围着子宫内膜，二者在维持妊娠中都起着重要作用。子宫内膜是一种性类固醇靶组织，由上皮细胞（腔上皮、腺上皮）被多细胞间质包围组成，后者包含一个广泛的血管腔室以及波动的免疫细胞群体，这些免疫细胞在调节组织功能中起重要作用。MCs在人类子宫中的作用了解甚少，对其调节或类固醇对其分化状态的影响知之甚少。当前研究有两个目的：1）研究子宫MCs的时空定位并确定其表型；2）确定MCs是否表达与子宫功能相关的类固醇受体，包括雌激素（ERα、ERβ）、孕激素（PR）和糖皮质激素（GR）。来自女性（n = 46）的组织样本用于RNA提取（n = 26）或固定（n = 20）用于免疫组织化学。在子宫内膜组织匀浆中检测到由（类胰蛋白酶）和（类糜蛋白酶）编码的信使RNA。免疫组织化学显示类胰蛋白酶MCs的相对丰度为肌层>子宫内膜基底层>功能层子宫内膜。我们首次表明子宫MCs主要是经典的MC亚型：（阳性，+；阴性，-）类胰蛋白酶+/类糜蛋白酶-和类胰蛋白酶+/类糜蛋白酶+，但也鉴定出第三种亚型（类胰蛋白酶-/类糜蛋白酶+）。类胰蛋白酶+ MCs具有ERβ+/ERα-/PR-/GR+表型，与其他子宫免疫细胞群体（包括自然杀伤细胞）相似。子宫内膜组织驻留免疫MCs有三种蛋白酶特异性表型。MCs中ERβ和GR的表达与子宫内膜中其他免疫细胞的表达相似，表明MC功能可能会被局部类固醇微环境改变。
