Maternal circadian rhythm disruption affects neonatal inflammation via metabolic reprograming of myeloid cells
Maternal circadian rhythm disruption affects neonatal inflammation via metabolic reprograming of myeloid cells

Maternal circadian rhythm disruption affects neonatal inflammation via metabolic reprograming of myeloid cells

Nat Metab. 2024 Apr 1. doi: 10.1038/s42255-024-01021-y. Online ahead of print.

ABSTRACT

Disruption of circadian rhythm during pregnancy produces adverse health outcomes in offspring; however, the role of maternal circadian rhythms in the immune system of infants and their susceptibility to inflammation remains poorly understood. Here we show that disruption of circadian rhythms in pregnant mice profoundly aggravates the severity of neonatal inflammatory disorders in both male and female offspring, such as necrotizing enterocolitis and sepsis. The diminished maternal production of docosahexaenoic acid (DHA) and the impaired immunosuppressive function of neonatal myeloid-derived suppressor cells (MDSCs) contribute to this phenomenon. Mechanistically, DHA enhances the immunosuppressive function of MDSCs via PPARĪ³-mediated mitochondrial oxidative phosphorylation. Transfer of MDSCs or perinatal supplementation of DHA relieves neonatal inflammation induced by maternal rhythm disruption. These observations collectively demonstrate a previously unrecognized role of maternal circadian rhythms in the control of neonatal inflammation via metabolic reprograming of myeloid cells.

PMID:38561509 | DOI:10.1038/s42255-024-01021-y