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

Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine

iScienceLast synced 8/30/2026Status: syncedPMID: 42667065 pmidDOI: 10.1016/j.isci.2026.117295

Summary 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 promotesupregulation 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. abs0010 Graphical abstract http://www.w3.org/1999/xlink float portrait ga1.webp undfig1 anchor portrait graphical abs0015 Highlights • Maternal obesity induces immunosuppression in the developing fetal liver u0010 • Spp1 promotes placental-fetal liver TGFβ crosstalk in maternal obesity u0015 • TGFβ pathways and Rbl2 upregulation link to T cell G1 phase arrest u0020 simple ulist0010 author-highlights abs0020 Biological sciences; Components of the immune system; Immune response; Immune system; Immunity; Immunology teaser abs0025

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