威尔康奈尔医学院Melody Y. Zeng课题组的一项最新研究示了肠道菌群促进母胎界面的免疫耐受。相关论文于2025年12月17日发表于国际顶尖学术期刊《细胞》杂志上。
该课题组证明了妊娠小鼠的肠-胎盘免疫轴，其中肠道微生物群的缺失或扰动会失调母体在MFI的IFN-γ和IL-17反应，导致胎儿吸收。微生物依赖的色氨酸衍生物分别通过启动髓源性抑制细胞（MDSCs）和肠源性RORγt+调节性T细胞（Tregs），在MFI抑制IFN-γ+和IL-17+ T细胞。色氨酸衍生物吲哚-3-甲醇，或色氨酸代谢乳杆菌鼠乳杆菌，在MFI重新平衡T细胞反应，减少无菌小鼠的胎儿吸收。
此外，在人类复发性流产病例中，MDSCs、RORγt+ Tregs和微生物依赖的色氨酸衍生物在MFI处失调。总之，他们的发现确定了促进胎儿发育的微生物依赖的免疫耐受机制。
据悉，在母胎界面（MFI）免疫耐受是胎儿发育所必需的。过量的母体干扰素-γ (IFN-γ)和白细胞介素-17 （IL-17）与妊娠并发症有关，但母体IFN-γ和IL-17在MFI中的调节尚不清楚。
附：英文原文
Title: Gut microbiota promotes immune tolerance at the maternal-fetal interface
Author: Julia A. Brown, Mohammed Amir, Shui Yu, Daniel S.H. Wong, Jinghua Gu, Uthra Balaji, Christopher N. Parkhurst, Seunghee Hong, Lucy R. Hart, Hannah C. Carrow, Mamadou A. Bah, Aparna Ananthanarayanan, Katherine Z. Sanidad, Mengze Lyu, Anisa Siddikova, Marina Lima Silva Santos, Inna Serganova, Gretchen E. Diehl, Josef Anrather, Naohiro Inohara, Gregory F. Sonnenberg, Virginia Pascual, Melody Y. Zeng
Issue&Volume: 2025-12-17
Abstract: Immune tolerance at the maternal-fetal interface (MFI) is required for fetal development. Excessive maternal interferon-gamma (IFN-γ) and interleukin-17 (IL-17) are linked to pregnancy complications, but the regulation of maternal IFN-γ and IL-17 at the MFI is poorly understood. Here, we demonstrate a gut-placenta immune axis in pregnant mice in which the absence or perturbation of gut microbiota dysregulates maternal IFN-γ and IL-17 responses at the MFI, resulting in fetal resorption. Microbiota-dependent tryptophan derivatives suppress IFN-γ+ and IL-17+ T cells at the MFI by priming myeloid-derived suppressor cells (MDSCs) and gut-derived RORγt+ regulatory T cells (Tregs), respectively. The tryptophan derivative indole-3-carbinol, or tryptophan-metabolizing Lactobacillus murinus, rebalances the T cell response at the MFI and reduces fetal resorption in germ-free mice. Furthermore, MDSCs, RORγt+ Tregs, and microbiota-dependent tryptophan derivatives are dysregulated at the MFI in human recurrent miscarriage cases. Together, our findings identify microbiota-dependent immune tolerance mechanisms that promote fetal development.
DOI: 10.1016/j.cell.2025.11.022
Source: https://www.cell.com/cell/abstract/S0092-8674(25)01318-2