| First Author | Li Y | Year | 2024 |
| Journal | Circulation | Volume | 149 |
| Issue | 21 | Pages | 1670-1688 |
| PubMed ID | 38314577 | Mgi Jnum | J:358819 |
| Mgi Id | MGI:7781967 | Doi | 10.1161/CIRCULATIONAHA.123.064391 |
| Citation | Li Y, et al. (2024) A Galectin-9-Driven CD11c(high) Decidual Macrophage Subset Suppresses Uterine Vascular Remodeling in Preeclampsia. Circulation 149(21):1670-1688 |
| abstractText | BACKGROUND: Preeclampsia is a serious disease of pregnancy that lacks early diagnosis methods or effective treatment, except delivery. Dysregulated uterine immune cells and spiral arteries are implicated in preeclampsia, but the mechanistic link remains unclear. METHODS: Single-cell RNA sequencing and spatial transcriptomics were used to identify immune cell subsets associated with preeclampsia. Cell-based studies and animal models including conditional knockout mice and a new preeclampsia mouse model induced by recombinant mouse galectin-9 were applied to validate the pathogenic role of a CD11c(high) subpopulation of decidual macrophages (dMphi) and to determine its underlying regulatory mechanisms in preeclampsia. A retrospective preeclampsia cohort study was performed to determine the value of circulating galectin-9 in predicting preeclampsia. RESULTS: We discovered a distinct CD11c(high) dMphi subset that inhibits spiral artery remodeling in preeclampsia. The proinflammatory CD11c(high) dMphi exhibits perivascular enrichment in the decidua from patients with preeclampsia. We also showed that trophoblast-derived galectin-9 activates CD11c(high) dMphi by means of CD44 binding to suppress spiral artery remodeling. In 3 independent preeclampsia mouse models, placental and plasma galectin-9 levels were elevated. Galectin-9 administration in mice induces preeclampsia-like phenotypes with increased CD11c(high) dMphi and defective spiral arteries, whereas galectin-9 blockade or macrophage-specific CD44 deletion prevents such phenotypes. In pregnant women, increased circulating galectin-9 levels in the first trimester and at 16 to 20 gestational weeks can predict subsequent preeclampsia onset. CONCLUSIONS: These findings highlight a key role of a distinct perivascular inflammatory CD11c(high) dMphi subpopulation in the pathogenesis of preeclampsia. CD11c(high) dMphi activated by increased galectin-9 from trophoblasts suppresses uterine spiral artery remodeling, contributing to preeclampsia. Increased circulating galectin-9 may be a biomarker for preeclampsia prediction and intervention. |
