To a certain extent, pregnancy is equivalent to successful allotransplantation, and considerable effort has been invested in understanding the mechanism of maternal-fetal immune tolerance, which has always been a hot research topic. During normal pregnancy, the fetus carrying the paternal human leukocyte antigen (HLA) stimulates the maternal immune system to develop immune tolerance so as to maintain normal development of the fetus and placenta, instead of activating various immune cells to participate in the rejection reaction. Precise regulation of decidual immune cells, for example, dynamics between M1 and M2 macrophages (Zhang et al., 2017), and induction of regulatory T cells (Tregs) play an essential role in maternal-fetal immune tolerance (Krop et al., 2020).

Cytokines and chemokines mediate an immune microenvironment at the maternal-fetal interface established by immune cells (Engert et al., 2007, Szarka et al., 2010). Studies have shown that trophoblasts and a variety of immune cells such as decidual macrophages (DMs), decidual dendritic (dDC) cells, and decidual natural killer (dNK) cells secrete IL-10 (Gregori et al., 2010, Hanna et al., 2000, Lidström et al., 2003). Furthermore, as a multifunctional immunosuppressive factor, IL-10 can regulate various immune cell functions and is essential for normal pregnancy (Cheng and Sharma, 2015). For example, IL-10 induces differentiation of DMs to regulate dNK cell toxicity and activation. Meanwhile, the link between IL-10 and metabolism is also becoming increasingly evident. Inhibiting endogenous production of IL-10 in mice having non-alcoholic fatty liver increases the expression of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), IL-6, and IL-1β, and is accompanied by enhanced lipid synthesis and storage proteins as well as impaired insulin signal transduction in the liver (Cintra et al., 2008). A high-fat diet induces adipocyte hypertrophy in epididymal and inguinal white adipose tissues as well as fat accumulation in the liver, which can be blocked by promoting IL-10 expression. Moreover, IL-10 can maintain insulin sensitivity and relieve glucose intolerance (Gao et al., 2013). In addition to improving insulin action and signaling activity, an earlier study showed that IL-10 increased whole-body lipid synthesis and skeletal muscle glycolysis, and decreased intramuscular fatty acyl-CoA levels (Kim et al., 2004). Low circulating levels of IL-10 in obese women were associated with the metabolic syndrome; this result is similar to a report suggesting that reduced IL-10 expression is present in serum and adipose tissue of obese children with hypertriglyceridemia (Esposito et al., 2003, Liu et al., 2018). Relationship between IL-10 and metabolism or maternal-fetal immune tolerance has led to a speculation that there might be a link between the latter two, and that IL-10 may play a bridging role.

This review focuses on the functional regulation of IL-10 in pregnancy and illustrates the role of IL-10 in the induction of maternal-fetal immune tolerance. In addition, based on studies in other disciplinary areas of research, a bold speculation is made on the role of IL-10 in pregnancy, that is, metabolism regulates IL-10 secretion and also mediates the regulation of immune cell function by IL-10.