Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, Vic., Australia.
Department of Molecular and Translational Sciences, School of Clinical Sciences, Monash University, Clayton, Vic., Australia.
Andrology. 2019 Sep;7(5):703-711. doi: 10.1111/andr.12682. Epub 2019 Jul 19.
The interface between the epididymis and the immune system is implicated in many male reproductive pathologies. The resident immune cell populations and immune-environment within the epididymis are significantly different from the testis, which is an immune-privileged site. Moreover, the immune cell subsets and immunological responses between different regions of the epididymis vary considerably. The cauda epididymis is more susceptible to autoimmune responses than the caput in rodent models of active immunization or suppressed immune tolerance, and in men with congenital or physical damage to the reproductive tract. Activins are members of the transforming growth factor-β family of cytokines that are crucial for testis and epididymal development; however, they also have complex immunoregulatory properties and may play an essential role in the regulation of immunity in the reproductive tract.
Our recent research and relevant publications by other researchers identified following a PubMed search are reviewed.
The caput epididymis displays elevated endogenous expression of activins A and B and the immunoregulatory gene, indoleamine-2,3-dioxygenase, co-existing with an extensive population of intra-epithelial and interstitial macrophages and dendritic cells, which appear to be involved in regulating tolerance against sperm antigens. The caput is also relatively resistant to inflammatory damage caused by autoimmunity or bacterial infection, but the cauda, which exhibits low activin expression and high levels of the activin-binding protein, follistatin, is highly susceptible to inflammatory damage. Paradoxically, inflammation in the cauda induces increased activin production, and inhibition of activin activity reduces inflammatory responses. Studies using mouse models with altered levels of activins and follistatin indicate a relationship between the activins and genes involved in inflammation and immunoregulation.
The existing data indicate that activins play a complex role in controlling inflammation and immunity in the epididymis and vas deferens.
附睾与免疫系统的界面与许多男性生殖病理学有关。附睾内的常驻免疫细胞群体和免疫环境与睾丸明显不同，睾丸是一个免疫特权部位。此外，附睾不同区域的免疫细胞亚群和免疫反应也有很大差异。在主动免疫或免疫抑制耐受的啮齿动物模型中，以及在生殖道先天性或物理损伤的男性中，附睾尾部比头部更容易受到自身免疫反应的影响。激活素是转化生长因子-β细胞因子家族的成员，对睾丸和附睾的发育至关重要；然而，它们也具有复杂的免疫调节特性，可能在生殖系统免疫调节中发挥重要作用。
我们最近的研究和其他研究人员的相关出版物，是通过 PubMed 搜索进行综述的。
附睾头部显示出激活素 A 和 B 以及免疫调节基因吲哚胺 2,3-双加氧酶的内源性高表达，同时存在大量上皮内和间质巨噬细胞和树突状细胞，这些细胞似乎参与调节对精子抗原的耐受。头部对自身免疫或细菌感染引起的炎症损伤也相对具有抗性，但尾部，其激活素表达较低，激活素结合蛋白 follistatin 水平较高，对炎症损伤高度敏感。矛盾的是，尾部的炎症会诱导激活素的产生增加，而抑制激活素的活性会减少炎症反应。使用激活素和 follistatin 水平改变的小鼠模型进行的研究表明，激活素与参与炎症和免疫调节的基因之间存在关系。
现有数据表明，激活素在控制附睾和输精管的炎症和免疫方面发挥着复杂的作用。
