Human fetal dendritic cells promote prenatal T-cell immune suppression through arginase-2

Prenatal immune suppression is regulated by fetal arginase-2-expressing dendritic cells which respond normally to toll-like receptor stimulation but, in contrast to adult dendritic cells, induce regulatory T cells and repress TNF-α secretion by effector T cells. How the immune system of a developing fetus responds to maternal and microbial antigens is not well understood. Florent Ginhoux and colleagues show that pre-natal immune suppression is regulated by fetal arginase-expressing dendritic cells, which respond normally to toll-like receptor stimulation but, in contrast to adult dendritic cells, induce regulatory rather than effector T cells. During gestation the developing human fetus is exposed to a diverse range of potentially immune-stimulatory molecules including semi-allogeneic antigens from maternal cells1,2, substances from ingested amniotic fluid3,4, food antigens5, and microbes6. Yet the capacity of the fetal immune system, including antigen-presenting cells, to detect and respond to such stimuli remains unclear. In particular, dendritic cells, which are crucial for effective immunity and tolerance, remain poorly characterized in the developing fetus. Here we show that subsets of antigen-presenting cells can be identified in fetal tissues and are related to adult populations of antigen-presenting cells. Similar to adult dendritic cells, fetal dendritic cells migrate to lymph nodes and respond to toll-like receptor ligation; however, they differ markedly in their response to allogeneic antigens, strongly promoting regulatory T-cell induction and inhibiting T-cell tumour-necrosis factor-α production through arginase-2 activity. Our results reveal a previously unappreciated role of dendritic cells within the developing fetus and indicate that they mediate homeostatic immune-suppressive responses during gestation.