Abstract:

Recurrent spontaneous abortion (RSA) is a common pregnancy-associated disorder in women of childbearing age. The etiology of RSA is complex, and the imbalance of immune cell homeostasis at the maternal-fetal interface represents a key pathogenic mechanism. This review summarizes the abnormal changes of major immune cell subsets and their interaction networks in RSA. T cell dysfunction is characterized by the following aspects: the reduced number and impaired function of regulatory T cells (Treg cells), especially CCR8+ decidual Treg cells; the abnormal activation of helper T cells 1 (Th1 cells) and Th17 cells; the dysfunction of immune checkpoints in CD8+ T cells; and the metabolically abnormal activation of γδT cells. Collectively, these disorders disrupt the immune tolerance at the maternal-fetal interface. Decidual natural killer cells interfere with the vascular remodeling and inflammatory homeostasis through the imbalance of receptor-ligand signaling, the loss of exosomal regulatory function, and metabolic abnormalities. The polarization imbalance of M1/M2 macrophages and the dysfunction of the ENPP2-lysophosphatidic acid (LPA) autophagy axis also contribute to the pathogenesis of RSA. In addition, the decrease or functional impairment of decidual dendritic cells impairs their ability to induce immune tolerance. These immune cells form a regulatory network, and their mutual interactions create a vicious cycle that exacerbates inflammatory responses. To summarize the core pathogenic mechanisms of various immune cells may provide an important reference for further exploration of novel diagnostic markers and therapeutic targets for RSA.

Key words: T-lymphocytes, Macrophages, Recurrent spontaneous abortion, Natural killer cells, Decidual dendritic cells