德国慕尼黑工业大学Mikael Simons小组的一项最新研究发现了单细胞空间转录组分析定义了慢性活动性多发性硬化症病变的病原性炎症生态位。相关论文发表在2025年10月29日出版的《免疫学》杂志上。

小组通过将单核RNA测序（snRNA-seq）与多路错误荧光原位杂交（MERFISH）相结合，生成了此类病变的高分辨率单细胞分子和空间图谱。在病变边缘，研究人员发现与炎症小胶质细胞相关的CD8⁺ T细胞龛显示干扰素反应和上调脂质代谢。为了研究它们的功能，该研究团队在实验性自身免疫性脑脊髓炎（EAE）小鼠的小胶质细胞中删除了ATP结合盒转运蛋白A1和G1 (ABCA1/G1)，这增加了脂质储存吞噬细胞的形成，从而放大了炎症。

此外，药物靶向固醇代谢可减轻EAE中泡沫细胞的形成和炎症性脱髓鞘。他们在慢性活动性多发性硬化症病变中免疫龛的高分辨率图谱确定了脂质储存、功能失调的小胶质细胞在持续性神经炎症中的作用。

据了解，区隔性炎症是多发性硬化症（MS）进展的关键驱动因素，但维持其持续性的机制尚不清楚。这种持续和缓慢发展的炎症过程的一个标志是慢性活动性MS病变。

附：英文原文

Title: Single-cell spatial transcriptomic profiling defines a pathogenic inflammatory niche in chronic active multiple sclerosis lesions

Author: Ruoqing Feng, Lena Spieth, Lu Liu, Stefan Berghoff, Jonas Franz, Qian Liu, Zhen Wang, Vini Tiwari, Simona Vitale, Simon Frerich, Sergi Florensa, Niklas Junker, Ludwig Huber, Marco Keller, Christoph Müller, Franz Bracher, Xiaoke Ge, Patrick C.N. Rensen, Gijs Kooij, Leon Hosang, Serhii Chornyi, Martin Dichgans, Ozgun Gokce, Gesine Saher, Christine Stadelmann, Martin Giera, Janos Groh, Mikael Simons

Issue&Volume: 2025-10-29

Abstract: Compartmentalized inflammation is a key driver of multiple sclerosis (MS) progression, but the mechanisms sustaining its persistence remain unclear. A hallmark of this persistent and slowly evolving inflammatory process is chronic active MS lesions. We generated a high-resolution, single-cell molecular and spatial atlas of such lesions by combining single-nucleus RNA sequencing (snRNA-seq) with multiplexed error-robust fluorescence in situ hybridization (MERFISH). Within lesion rims, we identified CD8+ T cell niches associated with inflamed microglia displaying an interferon response and upregulated lipid metabolism. To investigate their function, we deleted ATP-binding cassette transporters A1 and G1 (ABCA1/G1) in the microglia of mice with experimental autoimmune encephalomyelitis (EAE), which increased the formation of lipid-storing phagocytes that amplified inflammation. Moreover, pharmacologically targeting sterol metabolism mitigated foam cell formation and inflammatory demyelination in EAE. Thus, our high-resolution map of immune niches in chronic active MS lesions identifies a role for lipid-storing, dysfunctional microglia in persistent neuroinflammation.

DOI: 10.1016/j.immuni.2025.10.003

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00433-9