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| 001 | 282602 | ||
| 005 | 20251211161418.0 | ||
| 024 | 7 | _ | |a 10.1016/j.immuni.2025.10.003 |2 doi |
| 024 | 7 | _ | |a pmid:41167189 |2 pmid |
| 024 | 7 | _ | |a 1074-7613 |2 ISSN |
| 024 | 7 | _ | |a 1097-4180 |2 ISSN |
| 037 | _ | _ | |a DZNE-2025-01360 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Feng, Ruoqing |0 P:(DE-2719)9002625 |b 0 |e First author |u dzne |
| 245 | _ | _ | |a Single-cell spatial transcriptomic profiling defines a pathogenic inflammatory niche in chronic active multiple sclerosis lesions. |
| 260 | _ | _ | |a [Cambridge, Mass.] |c 2025 |b Cell Press |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1765465695_17918 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a 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. |
| 536 | _ | _ | |a 351 - Brain Function (POF4-351) |0 G:(DE-HGF)POF4-351 |c POF4-351 |f POF IV |x 0 |
| 536 | _ | _ | |a 353 - Clinical and Health Care Research (POF4-353) |0 G:(DE-HGF)POF4-353 |c POF4-353 |f POF IV |x 1 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de |
| 650 | _ | 7 | |a CD8+ T cells |2 Other |
| 650 | _ | 7 | |a CD8+ tissue-resident memory T cells |2 Other |
| 650 | _ | 7 | |a glia |2 Other |
| 650 | _ | 7 | |a lipids |2 Other |
| 650 | _ | 7 | |a microglia |2 Other |
| 650 | _ | 7 | |a multiple sclerosis |2 Other |
| 650 | _ | 7 | |a myelin |2 Other |
| 650 | _ | 7 | |a neuroinflammation |2 Other |
| 650 | _ | 7 | |a spatial transcriptomics |2 Other |
| 650 | _ | 7 | |a ATP Binding Cassette Transporter 1 |2 NLM Chemicals |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a Multiple Sclerosis: immunology |2 MeSH |
| 650 | _ | 2 | |a Multiple Sclerosis: genetics |2 MeSH |
| 650 | _ | 2 | |a Multiple Sclerosis: pathology |2 MeSH |
| 650 | _ | 2 | |a Multiple Sclerosis: metabolism |2 MeSH |
| 650 | _ | 2 | |a Mice |2 MeSH |
| 650 | _ | 2 | |a Encephalomyelitis, Autoimmune, Experimental: immunology |2 MeSH |
| 650 | _ | 2 | |a Encephalomyelitis, Autoimmune, Experimental: genetics |2 MeSH |
| 650 | _ | 2 | |a Encephalomyelitis, Autoimmune, Experimental: pathology |2 MeSH |
| 650 | _ | 2 | |a Microglia: immunology |2 MeSH |
| 650 | _ | 2 | |a Microglia: metabolism |2 MeSH |
| 650 | _ | 2 | |a Single-Cell Analysis: methods |2 MeSH |
| 650 | _ | 2 | |a Transcriptome |2 MeSH |
| 650 | _ | 2 | |a Inflammation: immunology |2 MeSH |
| 650 | _ | 2 | |a Inflammation: genetics |2 MeSH |
| 650 | _ | 2 | |a Gene Expression Profiling |2 MeSH |
| 650 | _ | 2 | |a Mice, Inbred C57BL |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a CD8-Positive T-Lymphocytes: immunology |2 MeSH |
| 650 | _ | 2 | |a Female |2 MeSH |
| 650 | _ | 2 | |a ATP Binding Cassette Transporter 1: genetics |2 MeSH |
| 650 | _ | 2 | |a ATP Binding Cassette Transporter 1: metabolism |2 MeSH |
| 650 | _ | 2 | |a Lipid Metabolism |2 MeSH |
| 650 | _ | 2 | |a Chronic Disease |2 MeSH |
| 700 | 1 | _ | |a Spieth, Lena |0 P:(DE-2719)9002306 |b 1 |u dzne |
| 700 | 1 | _ | |a Liu, Lu |0 P:(DE-2719)9002890 |b 2 |u dzne |
| 700 | 1 | _ | |a Berghoff, Stefan |0 P:(DE-2719)9001700 |b 3 |u dzne |
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| 700 | 1 | _ | |a Wang, Zhen |0 P:(DE-2719)9003032 |b 6 |u dzne |
| 700 | 1 | _ | |a Tiwari, Vini |0 P:(DE-2719)9001975 |b 7 |u dzne |
| 700 | 1 | _ | |a Vitale, Simona |0 P:(DE-2719)9002093 |b 8 |u dzne |
| 700 | 1 | _ | |a Frerich, Simon |b 9 |
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| 700 | 1 | _ | |a Huber, Ludwig |0 P:(DE-2719)9003174 |b 12 |u dzne |
| 700 | 1 | _ | |a Keller, Marco |b 13 |
| 700 | 1 | _ | |a Müller, Christoph |b 14 |
| 700 | 1 | _ | |a Bracher, Franz |b 15 |
| 700 | 1 | _ | |a Ge, Xiaoke |b 16 |
| 700 | 1 | _ | |a Rensen, Patrick C N |b 17 |
| 700 | 1 | _ | |a Kooij, Gijs |b 18 |
| 700 | 1 | _ | |a Hosang, Leon |b 19 |
| 700 | 1 | _ | |a Chornyi, Serhii |b 20 |
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| 700 | 1 | _ | |a Gokce, Ozgun |0 P:(DE-2719)9002754 |b 22 |u dzne |
| 700 | 1 | _ | |a Saher, Gesine |b 23 |
| 700 | 1 | _ | |a Stadelmann, Christine |b 24 |
| 700 | 1 | _ | |a Giera, Martin |b 25 |
| 700 | 1 | _ | |a Groh, Janos |0 P:(DE-2719)9002589 |b 26 |u dzne |
| 700 | 1 | _ | |a Simons, Mikael |0 P:(DE-2719)2811642 |b 27 |e Last author |u dzne |
| 773 | _ | _ | |a 10.1016/j.immuni.2025.10.003 |g Vol. 58, no. 12, p. 2989 - 3005.e10 |0 PERI:(DE-600)2001966-X |n 12 |p 2989 - 3005.e10 |t Immunity |v 58 |y 2025 |x 1074-7613 |
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