Blocking OLFM4/galectin-3 axis in placental polymorphonuclear myeloid-derived suppressor cells triggers intestinal inflammation in newborns.
Int Immunopharmacol
; 133: 112058, 2024 May 30.
Article
in En
| MEDLINE
| ID: mdl-38613883
ABSTRACT
Fetal growth restriction (FGR) is a major cause of premature and low-weight births, which increases the risk of necrotizing enterocolitis (NEC); however, the association remains unclear. We report a close correlation between placental polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and NEC. Newborns with previous FGR exhibited intestinal inflammation and more severe NEC symptoms than healthy newborns. Placental PMN-MDSCs are vital regulators of fetal development and neonatal gut inflammation. Placental single-cell transcriptomics revealed that PMN-MDSCs populations and olfactomedin-4 gene (Olfm4) expression levels were significantly increased in PMN-MDSCs in later pregnancy compared to those in early pregnancy and non-pregnant females. Female mice lacking Olfm4 in myeloid cells mated with wild-type males showed FGR during pregnancy, with a decreased placental PMN-MDSCs population and expression of growth-promoting factors (GPFs) from placental PMN-MDSCs. Galectin-3 (Gal-3) stimulated the OLFM4-mediated secretion of GPFs by placental PMN-MDSCs. Moreover, GPF regulation via OLFM4 in placental PMN-MDSCs was mediated via hypoxia inducible factor-1α (HIF-1α). Notably, the offspring of mothers lacking Olfm4 exhibited intestinal inflammation and were susceptible to NEC. Additionally, OLFM4 expression decreased in placental PMN-MDSCs from pregnancies with FGR and was negatively correlated with neonatal morbidity. These results revealed that placental PMN-MDSCs contributed to fetal development and ameliorate newborn intestinal inflammation.
Full text:
1
Database:
MEDLINE
Main subject:
Placenta
/
Fetal Growth Retardation
/
Myeloid-Derived Suppressor Cells
Limits:
Animals
/
Female
/
Humans
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Male
/
Newborn
/
Pregnancy
Language:
En
Journal:
Int Immunopharmacol
Journal subject:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Year:
2024
Type:
Article
Affiliation country:
China