Immune system involvement in the regulation of ovarian function and augmentation of cancer
Immune system involvement in the regulation of ovarian function and augmentation of cancer
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DOI：
10.1002/jemt.20307
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发表时间：
2006-06-01
影响因子：
2.5
通讯作者：
Bukovsky, Antonin
中科院分区：
文献类型：
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作者：
Bukovsky, Antonin
越来越多的证据表明免疫系统和间充质-上皮相互作用在卵巢功能调节中的作用。间充质细胞产生的细胞因子可以刺激卵巢结构的发育和退化。我们在此报道，间充质细胞在上皮细胞（即血管周细胞和单核细胞衍生细胞（MDC））和上皮内 T 淋巴细胞之间释放表面分子，与胎儿和成人卵巢中的卵子发生和新初级卵泡的形成有关。这些活化的间充质细胞与卵巢表面上皮相互作用，卵巢表面上皮似乎是次级生殖细胞和颗粒细胞的来源。在从初级卵泡群中选择正在生长的次级卵泡期间，激活的周细胞和 MDC 也与刺激鞘膜发育有关。然而，在卵泡中期阶段选择期间优势卵泡的存活与间充质细胞缺乏活性和鞘膜发育迟缓有关，因为缺乏芳香酶的未成熟颗粒细胞无法抵抗高水平的鞘膜雄激素。一旦选定的卵泡成熟（卵泡晚期），它就会显示出鞘膜间充质细胞活性增强和先进的鞘膜发育。黄体 (CL) 发育伴随着血管周细胞和 MDC 的高活性。在成熟的CL和妊娠的CL中，黄体MDC和周细胞表现出稳定（不活跃）的状态。 CL 的消退与周细胞的消退、MDC 转化为树突状细胞、T 淋巴细胞浸润以及免疫球蛋白 G 与黄体细胞的结合有关。免疫球蛋白 M (IgM) 与年轻但不成熟的黄体细胞结合。在妊娠 CL 中，IgM 与黄体血管结合，但不与黄体细胞结合。回归 CL 显示 IgM 与黄体细胞和血管结合。在卵巢癌中，存在高度活化的 MDC，有时还存在活化的周细胞（低分化癌）。 IgM 结合与妊娠 CL 中观察到的相似。这些数据表明血管周细胞、MDC、T 细胞和免疫球蛋白可能在卵巢生理调节中发挥重要作用，并有助于卵巢癌生长的增强。
Increasing evidence indicates a role for the immune system and mesenchymal-epithelial interactions in the regulation of ovarian function. Cytokines produced by mesenchymal cells can stimulate development and regression of ovarian structures. We report here that mesenchymal cells releasing surface molecules among epithelial cells-namely vascular pericytes and monocyte-derived cells (MDC)-and intraepithelial T lymphocytes are associated with oogenesis and formation of new primary follicles in both fetal and adult human ovaries. These activated mesenchymal cells interact with the ovarian surface epithelium, which appears to be a source of secondary germ cells and granulosa cells. Activated pericytes and MDC are also associated with stimulation of thecal development during selection of growing secondary follicles from the cohort of primary follicles. However, survival of the dominant follicle during mid-follicular phase selection is associated with a lack of activity of mesenchymal cells and retardation of thecal development, since immature granulosa cells lacking aromatase are unable to resist high levels of thecal androgens. Once the selected follicle matures (late follicular phase), it shows enhanced activity of thecal mesenchymal cells and advanced thecal development. Corpus luteum (CL) development is accompanied by a high activity of vascular pericytes and MDC. In mature CL and CL of pregnancy, luteal MDC and pericytes show a stable (inactive) state. Regression of the CL is associated with regression of pericytes, transformation of MDC into dendritic cells, infiltration by T lymphocytes, and binding of immunoglobulin G to the luteal cells. The immunoglobulin M (IgM) binds to young but not mature luteal cells. In the CL of pregnancy, IgM binds to luteal vessels, but not to luteal cells. Regressing CL shows IgM binding to both luteal cells and vessels. In ovarian cancers, highly activated MDC and sometimes activated pericytes (poorly differentiated carcinomas) are present. IgM binding is similar to that seen in the CL of pregnancy. These data indicate that vascular pericytes, MDC, T cells, and immunoglobulins may play an important role in the regulation of ovarian physiology and contribute to the augmentation of ovarian cancer growth.