Abstract
The success of pregnancy relies on the fine adjustment of the maternal immune system to tolerate the allogeneic fetus. Trophoblasts carrying paternal antigens are the only fetal-derived cells that come into direct contact with the maternal immune cells at the maternal–fetal interface. The crosstalk between trophoblasts and decidual immune cells (DICs) via cell–cell direct interaction and soluble factors such as chemokines and cytokines is a core event contributing to the unique immunotolerant microenvironment. Abnormal trophoblasts–DICs crosstalk can lead to dysregulated immune situations, which is well known to be a potential cause of a series of pregnancy complications including recurrent spontaneous abortion (RSA), which is the most common one. Immunotherapy has been applied to RSA. However, its development has been far less rapid or mature than that of cancer immunotherapy. Elucidating the mechanism of maternal–fetal immune tolerance, the theoretical basis for RSA immunotherapy, not only helps to understand the establishment and maintenance of normal pregnancy but also provides new therapeutic strategies and promotes the progress of immunotherapy against pregnancy-related diseases caused by disrupted immunotolerance. In this review, we focus on recent progress in the maternal–fetal immune tolerance mediated by trophoblasts–DICs crosstalk and clinical application of immunotherapy in RSA. Advancement in this area will further accelerate the basic research and clinical transformation of reproductive immunity and tumor immunity.
Highlights
A new life begins when an egg and a sperm meet at the ampulla of the mother’s fallopian tube and combine to form a fertilized egg, which further develops into a blastocyst
All the results suggest that the checkpoint T cell immunoglobulin mucin receptor 3 (Tim-3)-mediated signaling plays a role in the trophoblasts–Decidual natural killer (dNK) cells communication
We found that the receptor activator for nuclear factor-κ B ligand (RANKL), expressed by decidual stromal cells (DSCs) and in particular trophoblasts, interacted with RANK on dM and activated the downstream AKT/signal transducer and activator of transcription (STAT)-6 signaling, inducing M2 polarization, which further induced CD4+ T cells to present a Th2 bias [56]
Summary
A new life begins when an egg and a sperm meet at the ampulla of the mother’s fallopian tube and combine to form a fertilized egg, which further develops into a blastocyst. Interaction Between Trophoblasts and dNK Cells in Maternal–Fetal Tolerance Whether peripherally or locally, execution of cytotoxic and/or cytokine secretion functions of NK cells is dependent on the recognition of MHC ligands by their membrane surface receptor. Our team has demonstrated that the chemokine CXCL16 secreted by trophoblasts recruited peripheral monocytes to the decidua by interacting with the receptor CXCR6 [55] and promoted the polarization of macrophages into the M2 phenotype which exhibit decreased IL-15 production, so as to facilitate the inactivation of NK cells [39]. The research on maternal–fetal immunotolerance is to analyze the immunological truth behind successful pregnancy, but more importantly, it is expected to provide a new theoretical basis for the diagnosis and treatment of clinical pregnancyrelated complications caused by immune tolerance disorders including RSA.
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