The novel role of Hippo-YAP/TAZ in immunity at the mammalian maternal-fetal interface: Opportunities, challenges.

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.