Immunology and Infectious Diseases, Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79424, USA.
Department of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79424, USA.
Int J Mol Sci. 2023 Feb 8;24(4):3371. doi: 10.3390/ijms24043371.
Sertoli cells within the testis are instrumental in providing an environment for spermatogenesis and protecting the developing germ cells from detrimental immune responses which could affect fertility. Though these immune responses consist of many immune processes, this review focuses on the understudied complement system. Complement consists of 50+ proteins including regulatory proteins, immune receptors, and a cascade of proteolytic cleavages resulting in target cell destruction. In the testis, Sertoli cells protect the germ cells from autoimmune destruction by creating an immunoregulatory environment. Most studies on Sertoli cells and complement have been conducted in transplantation models, which are effective in studying immune regulation during robust rejection responses. In grafts, Sertoli cells survive activated complement, have decreased deposition of complement fragments, and express many complement inhibitors. Moreover, the grafts have delayed infiltration of immune cells and contain increased infiltration of immunosuppressive regulatory T cells as compared to rejecting grafts. Additionally, anti-sperm antibodies and lymphocyte infiltration have been detected in up to 50% and 30% of infertile testes, respectively. This review seeks to provide an updated overview of the complement system, describe its relationship with immune cells, and explain how Sertoli cells may regulate complement in immunoprotection. Identifying the mechanism Sertoli cells use to protect themselves and germ cells against complement and immune destruction is relevant for male reproduction, autoimmunity, and transplantation.
睾丸中的支持细胞在为精子发生提供环境以及保护发育中的生殖细胞免受可能影响生育能力的有害免疫反应方面起着重要作用。尽管这些免疫反应包含许多免疫过程，但本综述重点关注研究不足的补体系统。补体由 50 多种蛋白质组成，包括调节蛋白、免疫受体和一系列蛋白水解裂解，导致靶细胞破坏。在睾丸中，支持细胞通过创造免疫调节环境来防止生殖细胞发生自身免疫破坏。大多数关于支持细胞和补体的研究都是在移植模型中进行的，这些模型在研究强烈排斥反应期间的免疫调节非常有效。在移植物中，支持细胞在激活的补体中存活，补体片段的沉积减少，并且表达许多补体抑制剂。此外，与排斥移植物相比，移植物的免疫细胞浸润延迟，并且含有更多的免疫抑制性调节性 T 细胞浸润。此外，多达 50%的不育睾丸中检测到抗精子抗体，多达 30%的不育睾丸中检测到淋巴细胞浸润。本综述旨在提供补体系统的最新概述，描述其与免疫细胞的关系，并解释支持细胞如何在免疫保护中调节补体。确定支持细胞用来保护自身和生殖细胞免受补体和免疫破坏的机制与男性生殖、自身免疫和移植有关。
