Treg cells retain stable lineage commitment during pregnancy in mice after late gestation inflammatory challenge

T regulatory (Treg) cells are essential mediators of maternal fetal tolerance and are critical for constraining uterine inflammation. In some tissue settings, loss of Foxp3 expression can cause instability in Treg cell lineage commitment, elevated production of proinflammatory cytokines, and compromised suppressive function.

Whether preterm birth susceptibility is associated with loss of lineage fidelity and adoption of pro-inflammatory phenotypes in Treg cells is unknown. In this study, we investigated the lineage stability of Treg cells in vivo in mice using a Foxp3 fate-mapping system and models of preterm birth induced by late-gestation inflammatory challenge with lipopolysaccharide (LPS) or interleukin-1β (IL-1β). Ex-Foxp3-expressing (exFoxp3) cells were observed in the uterus-draining lymph nodes (udLNs) in non-pregnant mice and in similar abundance across normal gestation, and a proportion expressed pro-inflammatory cytokines IFNγ and/or IL-17A.