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 PPARγ-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.

怀孕期间昼夜节律的破坏会给后代带来不良的健康结果；然而，母亲昼夜节律在婴儿免疫系统中的作用及其对炎症的易感性仍然知之甚少。在这里，我们发现怀孕小鼠昼夜节律的破坏会严重加剧雄性和雌性后代的新生儿炎症性疾病的严重程度，例如坏死性小肠结肠炎和败血症。母体二十二碳六烯酸 (DHA) 产量的减少和新生儿骨髓源性抑制细胞 (MDSC) 的免疫抑制功能受损导致了这一现象。从机制上讲，DHA 通过 PPARγ 介导的线粒体氧化磷酸化增强 MDSC 的免疫抑制功能。转移 MDSC 或围产期补充 DHA 可缓解母体节律紊乱引起的新生儿炎症。这些观察结果共同证明了母体昼夜节律通过骨髓细胞代谢重编程控制新生儿炎症的作用，这一作用此前未被认识到。