A placental and fetal liver TGFβ signaling axis drives fetal immunosuppression in maternal obesity.

Maternal obesity (MO) impairs immunological development in the offspring with poorly defined mechanisms. By integrating single-cell RNA sequencing datasets from placentas and fetal livers of diet-induced obese mice, data showed that MO markedly enhances inflammatory and immune activation within the placenta but induces immunosuppression in fetal liver. Inter-organ cell-cell communication analysis further revealed that placental Spp1 signaling sent by macrophage potentiates TGFβ/Smad signaling in fetal liver immune cells, which promotes Rbl2 upregulation and induces a G1 phase arrest in T cells and basophils. Finally, T cell function is inhibited by MO. Totally, this study identifies a potential placental-fetal liver Spp1-TGFβ-Rbl2 axis associated with fetal immunosuppression due to MO.