Th17/Treg Cell Imbalance May Contribute to Spontaneous Preterm Labor

Abstract

Spontaneous preterm labor (SPTL) is a major cause of neonatal mortality and severe complications. T cells play a crucial role in mediating inflammation and immune tolerance at the maternal-fetal interface. T helper 17 cells (Th17, pro-inflammatory) and regulatory T cells (Treg, anti-inflammatory) are two subsets of CD4⁺ T cells with opposite functions, and their balance is important for maintaining immune homeostasis. Since infection and inflammation represent prominent factors responsible for the pathogenesis of SPTL, Th17/Treg imbalance at the maternal-fetal interface may trigger proinflammatory responses, potentially leading to SPTL. In this review, evidence from both clinical cases of SPTL and animal models indicates the presence of Th17/Treg imbalance in both peripheral blood and the maternal-fetal interface. Additionally, interleukin-6 (IL-6), interleukin-1β (IL-1β), and interleukin-8 (IL-8) have been involved in the pathogenesis of inflammation-induced SPTL, suggesting that Th17/Treg imbalance may have relevance to and be involved in the pathogenic process of SPTL. Moreover, the presence of Th17/Treg imbalance in risk factors for SPTL, such as autoimmune diseases and bacterial infections, further supports this connection indirectly. Although predictive models and interventional strategies related to SPTL have been explored, there is currently insufficient evidence to establish a direct causal relationship between Th17/Treg imbalance and the onset of SPTL.

Keywords: Th17; Treg; balance; spontaneous preterm labor.

Figure 1

The proposed mechanism for the induction of SPTL by Th17/Treg imbalance is as follows: progesterone facilitates the differentiation of Treg cells and concurrently impedes the differentiation of Th17 cells within the peripheral blood or the maternal–fetal interface through IL-10 to maintain a healthy pregnancy. Conversely, autoimmune disease or infection triggers the production of factors IL-6 and IL-1β, leading to Th17 differentiation (promoting IL-8 secretion) and suppressing Treg differentiation, ultimately resulting in SPTL.