加拿大多伦多儿童医院Brian T. Kalish团队取得一项新突破。他们的研究显示，发育中的小鼠脑免疫景观的空间转录组学揭示了母体免疫激活和微生物组耗竭的影响。这一研究成果发表在2026年1月6日出版的国际学术期刊《自然—神经科学》上。

本研究采用多路原位空间转录组学方法测定了妊娠中后期无主性脑发育过程中主要免疫配体和受体的表达。考虑到母体环境在塑造胎儿神经发育中的重要性，研究组确定了母体免疫激活（MIA）和母体微生物群消耗后胚胎神经免疫景观是如何改变的。他们的研究揭示了发育中的大脑中基因表达和空间结构的显著性别特异性模式。课题组人员观察到MIA和微生物组耗竭后CXCL12/CXCR7趋化因子网络的变化，提示神经祖细胞异常的潜在共同机制。这种抵抗强调了母体环境如何在发育中的大脑中精确调节免疫分子，突出了性别特异性的脆弱性。

研究人员表示，免疫分子及其同源受体在大脑中受到发育调节，并在神经发育障碍的背景下动态表达。尽管免疫分子对大脑线路很重要，但在发育中的大脑中，缺乏神经免疫景观的全面地图。

附：英文原文

Title: Spatial transcriptomics of the developing mouse brain immune landscape reveals effects of maternal immune activation and microbiome depletion

Author: Kukreja, Bharti, Jeon, Shin, Cao, Wuxinhao, Rusu, Bianca, Harrison, Camille F., Ghazisaeidi, Shahrzad, Tahmasian, Nareh, Feng, Min Yi, Chan, Rita, Loan, Allison, Johnston, William B., Padhy, Shreya, Rakoff-Nahoum, Seth, Wang, Jing, Yim, Yeong Shin, Kalish, Brian T.

Issue&Volume: 2026-01-06

Abstract: Immune molecules and their cognate receptors are developmentally regulated in brain and dynamically expressed in the context of neurodevelopmental disorders. Despite the importance of immune molecules to brain wiring, a comprehensive map of the neuroimmune landscape is lacking in developing brain. Here we employed multiplexed in situ spatial transcriptomics to measure the expression of major immune ligands and receptors in developing mouse brain during mid and late gestation. Given the importance of maternal environment in shaping fetal neurodevelopment, we determined how embryonic neuroimmune landscape was altered after maternal immune activation (MIA) and maternal microbiome depletion. Our study revealed notable sex-specific patterns in gene expression and spatial architecture within developing brain. We observed changes in the CXCL12/CXCR7 chemokine network after MIA and microbiome depletion, suggesting a potential common mechanism underlying neural progenitor abnormalities. This resource underscores how the maternal environment programs precise regulation of immune molecules in developing brain, highlighting sex-specific vulnerability.

DOI: 10.1038/s41593-025-02162-3

Source: https://www.nature.com/articles/s41593-025-02162-3