Classical reproductive immunology considers pregnancy to be similar to a semiallogeneic transplantation process owing to the presence of paternal class I HLA-C molecules on placental trophoblast cells of fetal origin, and the maintenance of normal pregnancy depends on maternal immune recognition and tolerance (Moffett and Loke, 2006). The placenta and decidua constitute the maternal-fetal interface, which is the microenvironment for the interaction between the cells of fetal and maternal origin. It is mainly composed of trophoblast cells, decidual stromal cells (DSCs), and decidual immune cells. These cells play key roles in the gestation process, including promoting trophoblast invasion and spiral artery remodeling, protecting the mother from harmful pathogens, and preventing the fetus from being attacked by the maternal immune system (Cha et al., 2012, Prabhudas et al., 2015).

Autophagy is a tightly regulated catabolic process that involves the degradation of cytoplasmic organelles and proteins in lysosomes. There are three types of autophagy depending on the mechanism of cargo transport to lysosomes: (i) Microautophagy, in which cytoplasmic material is transported to the lysosome via direct invagination or protrusion of the lysosomal membrane (Mijaljica et al., 2011). (ii) Chaperone-mediated autophagy, in which molecular chaperones restore intracellular proteins from the folded state to the unfolded state and transport them to the lysosome (Cuervo and Wong, 2014). (iii) Macroautophagy, in which the cargo is sequestered into a double-membrane organelle called the autophagosome and then transported to the lysosome to form autophagic lysosomes, where the cargo is degraded and recycled. New metabolites are generated during degradation and sent back to the cytoplasm to synthesize new macromolecules and generate energy (Levine and Klionsky, 2004, Morciano et al., 2021). Macroautophagy has been most extensively studied and is a piece of major machinery responsible for the degradation in cells. Thus, here we only focus on macroautophagy (hereafter referred to as autophagy). The autophagic flux consists of the following steps: initiation, nucleation, elongation, maturation, fusion with lysosomes, and degradation (Lamb et al., 2013) (Fig. 1).

Autophagy plays a crucial role in innate and adaptive immune responses (Matsuzawa-Ishimoto et al., 2018). Recent studies have shown that the autophagy pathway was involved in survival, apoptosis, differentiation, activation, and effector functions of immune cell subsets. Deleting multiple key molecules in the autophagy pathway could cause different phenotypes of immune dysfunction in mouse models. Therefore, autophagy has become a research hotspot in tumor immunology studies and has led to many breakthroughs (Xia et al., 2021, Deretic, 2021). The maternal-fetal interface microenvironment has been suggested to bear similarities to the tumor microenvironment. Current researches indicate that autophagy affects embryogenesis and implantation, and plays an important role in the maintenance of pregnancy (Nakashima et al., 2017, Nakashima et al., 2019). Although the effector relationship between autophagy and the decidual immune cells (e.g., natural killer cells, macrophages, and T cells) has been reported (Qin et al., 2022), the overall effect of autophagy on innate and adaptive immunity at the maternal-fetal interface has not been fully elucidated. In this review, we summarize recent findings on autophagy pathways in the immune microenvironment at the maternal-fetal interface, including those related to immune cells, immune response and immune tolerance molecules, which provides new insight into how autophagy participates in the regulation of immunity to establish and maintain the mother-fetal interface.