Fuma Kazuya, Iitani Yukako, Imai Kenji, Ushida Takafumi, Tano Sho, Yoshida Kosuke, Yokoi Akira, Miki Rika, Kidokoro Hiroyuki, Sato Yoshiaki, Hara Yuichiro, Ogi Tomoo, Nomaki Kohei, Tsuda Makoto, Komine Okiru, Yamanaka Koji, Kajiyama Hiroaki, Kotani Tomomi
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Division of Reproduction and Perinatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, Nagoya, Japan.
Commun Biol. 2025 Jan 17;8(1):75. doi: 10.1038/s42003-025-07511-3.
Histological chorioamnionitis (HCA) is a form of maternal immune activation (MIA) linked to an increased risk of neurodevelopmental disorders in offspring. Our previous study identified neurodevelopmental impairments in an MIA mouse model mimicking HCA. Thus, this study investigated the role of CD11c microglia, key contributors to myelination through IGF-1 production, in this pathology. In the mouse model, the CD11c microglial population was significantly lower in the MIA group than in the control group on postnatal day 3 (PN3d). Furthermore, myelination-related protein levels significantly decreased in the MIA group at PN8d. In humans, preterm infants with HCA exhibited higher IL-6 and IL-17A cord-serum levels and lower IGF-1 levels than those without HCA, followed by a higher incidence of delayed myelination on magnetic resonance imaging at the term-equivalent age. In silico analysis revealed that the transient induction of CD11c microglia during early development occurred similarly in mice and humans. Notably, a lack of high CD11c microglial population has been observed in children with neurodevelopmental disorders. This study reports impaired induction of CD11c microglia during postnatal development in a mouse model of MIA associated with delayed myelination. Our findings may inform strategies for improving outcomes in infants with HCA.
组织学绒毛膜羊膜炎（HCA）是一种母体免疫激活（MIA）形式，与后代神经发育障碍风险增加有关。我们之前的研究在模拟HCA的MIA小鼠模型中发现了神经发育损伤。因此，本研究调查了通过产生胰岛素样生长因子-1（IGF-1）对髓鞘形成起关键作用的CD11c小胶质细胞在这种病理过程中的作用。在该小鼠模型中，出生后第3天（PN3d）时，MIA组的CD11c小胶质细胞数量显著低于对照组。此外，在PN8d时，MIA组中与髓鞘形成相关的蛋白水平显著降低。在人类中，患有HCA的早产儿脐带血清中的白细胞介素-6（IL-6）和白细胞介素-17A（IL-17A）水平高于未患HCA的早产儿，而IGF-1水平较低，随后在足月等效年龄时磁共振成像显示髓鞘延迟形成的发生率更高。计算机分析显示，在小鼠和人类的早期发育过程中，CD11c小胶质细胞的短暂诱导情况相似。值得注意的是，在患有神经发育障碍的儿童中观察到缺乏高数量的CD11c小胶质细胞。本研究报告了在与髓鞘延迟形成相关的MIA小鼠模型中，出生后发育过程中CD11c小胶质细胞的诱导受损。我们的研究结果可能为改善患有HCA的婴儿的预后提供策略。
