Role of immune cells in the establishment of implantation and maintenance of pregnancy and immunomodulatory therapies for patients with repeated implantation failure and recurrent pregnancy loss

Background: Immune cells play an important role in the establishment of pregnancy, and abnormalities in the immune system can cause implantation failure and miscarriage. Methods: Previous papers have been summarized and the role of immune cells in reproduction is reviewed. Results: The immune environment in the uterus changes drastically from before implantation to after pregnancy to maintain pregnancy. In allogeneic pregnancies, immature dendritic cells (DCs) that induce immune tolerance from outside the uterus flow into the uterus, and mature DCs that remain in the uterus express programmed cell death ligand 2, which suppresses the immune response. Macrophages are classified into M1-macrophages, which induce inflammation, and M2-macrophages, which suppress inflammation; M1-macrophages are required for luteinization, and M2-macrophages induce the differentiation of endometrial epithelial cells to enable implantation. Regulatory T cells, which suppress rejection, are essential for the implantation and maintenance of allogeneic pregnancies. Implantation failure and fetal loss are associated with decreased numbers or qualitative abnormalities of DCs, macrophages, and regulatory T cells. The clinical usefulness of immunomodulatory therapies in patients with repeated implantation failure and recurrent pregnancy loss has been reported. Conclusion: The provision of individualized medical care in cases of implantation failure or miscarriage may improve clinical outcomes.