Laboratory for Reproductive Immunology, Hospital & Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai, China; The Academy of Integrative Medicine, Fudan University, Shanghai, China; Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Shanghai, China.
Pharmaceutical Outcomes Programme, British Columbia Children's Hospital, 938 West 28th Avenue, Vancouver BC, Canada.
Biomed Pharmacother. 2020 Jun;126:110061. doi: 10.1016/j.biopha.2020.110061. Epub 2020 Mar 4.
The Hippo-Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ), originally identified as a regulator of tissue generation and tumorigenesis, has been proven to have a pivotal position in immunity. Its multi-faceted roles in regulating immunity cover both intrinsic mechanism of immune cells and the crosstalk with non-immune cells. Survival of the allogeneic embryo in the maternal uterine environment depends on immune tolerance, supported by the highly orchestrated cooperation between decidual immune cells, decidual stromal cells and trophoblasts at the maternal-fetal interface. The abnormal maternal-fetal dialogue is believed to be associated with adverse pregnancy outcomes such as spontaneous pregnancy loss. Recent breakthroughs shed light on the how the Hippo-YAP/TAZ manipulate the decidualization and trophoblast invasion, while further research is needed to integrate and reconcile existing findings of the Hippo-YAP/TAZ in immunity and to extend them at the context of pregnancy. In this review, we summarized the Hippo-YAP/TAZ pathways, detailed the effects of YAP/TAZ on immune cells, and discussed the role of YAP/TAZ at the maternal-fetal interface and the potential of YAP/TAZ on immunity regulation at the context of pregnancy. Given the remarkable effect of therapeutic intervention of YAP/TAZ in cancer and autoimmune diseases, it is worthy to explore the response to YAP/TAZ inhibition in the maternal-fetal immunity. This may provide a new valuable target for therapy of pregnancy loss, or potentially other pregnancy complications.
Hippo-Yes 相关蛋白 (YAP)/含 PDZ 结合基序的转录共激活因子 (TAZ)，最初被确定为组织发生和肿瘤发生的调节剂，已被证明在免疫中具有关键地位。它在调节免疫中的多方面作用涵盖了免疫细胞的内在机制以及与非免疫细胞的串扰。同种异体胚胎在母体子宫环境中的存活依赖于免疫耐受，这得益于母体-胎儿界面上蜕膜免疫细胞、蜕膜基质细胞和滋养层细胞之间高度协调的合作。异常的母体-胎儿对话被认为与自然妊娠丢失等不良妊娠结局有关。最近的突破揭示了 Hippo-YAP/TAZ 如何操纵蜕膜化和滋养层浸润，而需要进一步的研究来整合和协调 Hippo-YAP/TAZ 在免疫中的现有发现，并将其扩展到妊娠背景下。在这篇综述中，我们总结了 Hippo-YAP/TAZ 途径，详细描述了 YAP/TAZ 对免疫细胞的影响，并讨论了 YAP/TAZ 在母体-胎儿界面的作用以及 YAP/TAZ 在妊娠背景下对免疫调节的潜力。鉴于 YAP/TAZ 治疗干预在癌症和自身免疫性疾病中的显著效果，值得探索 YAP/TAZ 抑制在母体-胎儿免疫中的反应。这可能为妊娠丢失或其他潜在妊娠并发症的治疗提供新的有价值的靶点。
