Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, United States.
Front Immunol. 2022 Jul 1;13:886645. doi: 10.3389/fimmu.2022.886645. eCollection 2022.
Immune regulation of female reproductive function plays a crucial role in fertility, as alterations in the relationship between immune and reproductive processes result in autoimmune subfertility or infertility. The breakdown of immune tolerance leads to ovulation dysfunction, implantation failure, and pregnancy loss. In this regard, immune cells with regulatory activities are essential to restore self-tolerance. Apart from regulatory T cells, double negative T regulatory cells (DNTregs) characterized by TCRαβ/γδCD3CD4CD8 (and negative for natural killer cell markers) are emerging as effector cells capable of mediating immune tolerance in the female reproductive system. DNTregs are present in the female reproductive tract of humans and murine models. However, their full potential as immune regulators is evolving, and studies so far indicate that DNTregs exhibit features that can also maintain tolerance in the female reproductive microenvironment. This review describes recent progress on the presence, role and mechanisms of DNTregs in the female reproductive system immune regulation and tolerance. In addition, we address how DNTregs can potentially provide a paradigm shift from the known roles of conventional regulatory T cells and immune tolerance by maintaining and restoring balance in the reproductive microenvironment of female fertility.
女性生殖功能的免疫调节在生育中起着至关重要的作用，因为免疫和生殖过程之间关系的改变会导致自身免疫性不孕或不育。免疫耐受的破坏导致排卵功能障碍、着床失败和妊娠丢失。在这方面，具有调节活性的免疫细胞对于恢复自身耐受至关重要。除了调节性 T 细胞（Treg 细胞），具有 TCRαβ/γδCD3CD4CD8（并且 NK 细胞标志物阴性）特征的双阴性 T 调节细胞（DNTregs）作为能够在女性生殖系统中介导免疫耐受的效应细胞而出现。DNTregs 存在于人类和鼠类模型的女性生殖道中。然而，它们作为免疫调节剂的全部潜力正在发展，迄今为止的研究表明，DNTregs 表现出的特征也可以在女性生殖微环境中维持耐受。本综述描述了 DNTregs 在女性生殖系统免疫调节和耐受中的存在、作用和机制的最新进展。此外，我们还探讨了 DNTregs 如何通过维持和恢复女性生育生殖微环境的平衡，为传统调节性 T 细胞和免疫耐受的已知作用提供范式转变。
