Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, South Australia, Australia.
Robinson Research Institute and School of Biomedicine, The University of Adelaide, Adelaide, South Australia, Australia.
Fertil Steril. 2022 Jun;117(6):1107-1120. doi: 10.1016/j.fertnstert.2022.04.023.
Immune cells are essential for endometrial receptivity to embryo implantation and early placental development. They exert tissue-remodeling and immune regulatory roles-acting to promote epithelial attachment competence, regulate the differentiation of decidual cells, remodel the uterine vasculature, control and resolve inflammatory activation, and suppress destructive immunity to paternally inherited alloantigens. From a biological perspective, the endometrial immune response exerts a form of "quality control"-it promotes implantation success when conditions are favorable but constrains receptivity when physiological circumstances are not ideal. Women with recurrent implantation failure and recurrent miscarriage may exhibit altered numbers or disturbed function of certain uterine immune cell populations-most notably uterine natural killer cells and regulatory T cells. Preclinical and animal studies indicate that deficiencies or aberrant activation states in these cells can be causal in the pathophysiological mechanisms of infertility. Immune cells are, therefore, targets for diagnostic evaluation and therapeutic intervention. However, current diagnostic tests are overly simplistic and have limited clinical utility. To be more informative, they need to account for the full complexity and reflect the range of perturbations that can occur in uterine immune cell phenotypes and networks. Moreover, safe and effective interventions to modulate these cells are in their infancy, and personalized approaches matched to specific diagnostic criteria will be needed. Here we summarize current biological understanding and identify knowledge gaps to be resolved before the promise of therapies to target the uterine immune response can be fully realized.
免疫细胞对于胚胎着床和早期胎盘发育的子宫内膜容受性至关重要。它们发挥组织重塑和免疫调节作用，促进上皮附着能力，调节蜕膜细胞的分化，重塑子宫血管，控制和解决炎症激活，并抑制对父系同种异体抗原的破坏性免疫。从生物学角度来看，子宫内膜免疫反应发挥了一种“质量控制”的作用——在条件有利时促进着床成功，但在生理环境不理想时限制接受能力。反复着床失败和反复流产的女性可能表现出某些子宫免疫细胞群体数量改变或功能紊乱——尤其是子宫自然杀伤细胞和调节性 T 细胞。临床前和动物研究表明，这些细胞的缺陷或异常激活状态可能是不孕的病理生理机制中的因果关系。因此，免疫细胞是诊断评估和治疗干预的目标。然而，目前的诊断测试过于简单，临床实用性有限。为了提供更全面的信息，它们需要考虑到免疫细胞表型和网络中可能发生的全部复杂性，并反映出一系列的扰动。此外，调节这些细胞的安全有效的干预措施还处于起步阶段，需要针对特定的诊断标准制定个性化的方法。在这里，我们总结了目前的生物学认识，并确定了在充分实现针对子宫免疫反应的治疗方法的承诺之前需要解决的知识空白。
