Foetal immune programming: hormones, cytokines, microbes and regulatory T cells

• Prenatal maternal environmental factors, significantly influence the foetal immune system.
• Various lines of evidence, including the foetal–maternal alignment of Treg cells, suggest that Treg cells are involved in foetal immune programming.
• Maternal and foetal Treg cells are likely to be influenced by cytokines, hormones and the gut microbiome.

In addition to genetic factors, environmental cues play important roles in shaping the immune system. The first environment that the developing foetal immune system encounters is the uterus. Although physically the mother and the foetus are separated by the placental membranes, various factors such as hormones and cytokines may provide “environmental cues” to the foetal immune system. Additionally, increasing evidence suggests that prenatal maternal environmental factors, particularly microbial exposure, might significantly influence the foetal immune system, affecting long-term outcomes, a concept termed foetal immune programming. Here we discuss the potential mediators of foetal immune programming, focusing on the role of pregnancy-related hormones, cytokines and regulatory T cells, which play a critical role in immune tolerance.