Yuan Xingxing, Li Chaofan, Yang Liuxin, Zhang Xiaoyu, Feng Xiaoling
First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, 150040, China.
Department of Medicine, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, 150006, China.
Immunol Res. 2025 Jul 21;73(1):108. doi: 10.1007/s12026-025-09664-z.
Recurrent pregnancy loss (RPL), defined as ≥ 2 consecutive losses, remains a significant clinical challenge with complex immunological underpinnings. While immune dysfunction underpins RPL, dendritic cells (DCs) emerge as central regulators of maternal-fetal tolerance. This review comprehensively explores the multifaceted roles of DC subsets at the maternal-fetal interface, including their contribution to immune tolerance, angiogenesis, placental development, and bidirectional interactions with trophoblasts and natural killer (NK) cells. We detail specific DC alterations in RPL, encompassing phenotypic shifts, functional defects, and disrupted DC-NK cell crosstalk, linking these changes to pregnancy loss risk. Emerging evidence highlights therapeutic strategies targeting DCs, such as tolerogenic DC vaccines and interventions modulating trophoblast MHC antigen presentation, alongside established immunomodulation, to restore immune balance. Underlying mechanisms like systemic inflammation impacting endometrial DCs are also discussed. By synthesizing current literature and controversies, this review elucidates the critical, yet complex, role of DC heterogeneity and function in RPL pathogenesis and discusses innovative interventions aimed at improving pregnancy outcomes.
复发性流产（RPL）定义为连续≥2次流产，仍然是一个具有复杂免疫学基础的重大临床挑战。虽然免疫功能障碍是RPL的基础，但树突状细胞（DCs）已成为母胎耐受的核心调节因子。本综述全面探讨了DC亚群在母胎界面的多方面作用，包括它们对免疫耐受、血管生成、胎盘发育以及与滋养层细胞和自然杀伤（NK）细胞双向相互作用的贡献。我们详细阐述了RPL中特定的DC改变，包括表型转变、功能缺陷以及DC-NK细胞串扰的破坏，将这些变化与流产风险联系起来。新出现的证据强调了针对DCs的治疗策略，如耐受性DC疫苗和调节滋养层MHC抗原呈递的干预措施，以及已有的免疫调节方法，以恢复免疫平衡。还讨论了全身炎症影响子宫内膜DCs等潜在机制。通过综合当前文献和争议内容，本综述阐明了DC异质性和功能在RPL发病机制中的关键但复杂的作用，并讨论了旨在改善妊娠结局的创新干预措施。
