Ulziibat Shirendeb, Ejima Kuniaki, Shibata Yasuaki, Hishikawa Yoshitaka, Kitajima Michio, Fujishita Akira, Ishimaru Tadayuki, Koji Takehiko
Division of Histology and Cell Biology, Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Sciences, Japan.
Hum Reprod. 2006 Sep;21(9):2281-9. doi: 10.1093/humrep/del176. Epub 2006 Jun 8.
Although intraepithelial lymphocytes (IELs) in human oviductal epithelium have been implicated in the regulation of local immunity, the precise kinetics and mechanism of steroid regulation of IEL are largely unknown.
We examined the localization of estrogen receptors (ERs) and progesterone receptors (PRs) in 41 human oviducts by immunohistochemistry. These tissues were obtained from various menstrual cycles, also from both post-menopausal women and tubal pregnancies. The expressions of ERbeta mRNA and membrane (m)PR mRNA were examined by in situ hybridization and RT-PCR, respectively.
Most of the IEL expressed ERbeta at both mRNA and protein levels. The number of ERbeta-positive IEL, which were identified as CD8-positive T lymphocytes and also were mPR positive, was increased in the late proliferative, the mid-secretory and late secretory phases in normally cycling women (P < 0.05). Interestingly, in tubal pregnancy, ERbeta-positive IELs were consistently abundant. In addition, we found a high Ki-67-labelling index for IEL, although ERalpha was entirely absent in the tubal pregnancy oviducts.
These results suggest that the number of IEL fluctuated because of estrogen and progesterone levels probably through ERbeta and mPR, respectively. ERbeta-positive IEL may be involved in regulating immune tolerance in tubal pregnancy oviducts.
尽管人输卵管上皮中的上皮内淋巴细胞(IELs)与局部免疫调节有关,但类固醇对IEL调节的精确动力学和机制在很大程度上尚不清楚。
我们通过免疫组织化学检查了41例人输卵管中雌激素受体(ERs)和孕激素受体(PRs)的定位。这些组织取自不同的月经周期,也来自绝经后妇女和输卵管妊娠患者。分别通过原位杂交和逆转录聚合酶链反应检测ERβ mRNA和膜(m)PR mRNA的表达。
大多数IEL在mRNA和蛋白质水平均表达ERβ。在正常月经周期的妇女中,被鉴定为CD8阳性T淋巴细胞且mPR也呈阳性的ERβ阳性IEL数量在增殖晚期、分泌中期和分泌晚期增加(P < 0.05)。有趣的是,在输卵管妊娠中,ERβ阳性IEL始终丰富。此外,我们发现IEL的Ki-67标记指数较高,尽管输卵管妊娠的输卵管中完全不存在ERα。
这些结果表明,IEL的数量可能分别通过ERβ和mPR因雌激素和孕激素水平而波动。ERβ阳性IEL可能参与调节输卵管妊娠输卵管中的免疫耐受。