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000282602 037__ $$aDZNE-2025-01360
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000282602 1001_ $$0P:(DE-2719)9002625$$aFeng, Ruoqing$$b0$$eFirst author$$udzne
000282602 245__ $$aSingle-cell spatial transcriptomic profiling defines a pathogenic inflammatory niche in chronic active multiple sclerosis lesions.
000282602 260__ $$a[Cambridge, Mass.]$$bCell Press$$c2025
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000282602 520__ $$aCompartmentalized inflammation is a key driver of multiple sclerosis (MS) progression, but the mechanisms sustaining its persistence remain unclear. A hallmark of this persistent and slowly evolving inflammatory process is chronic active MS lesions. We generated a high-resolution, single-cell molecular and spatial atlas of such lesions by combining single-nucleus RNA sequencing (snRNA-seq) with multiplexed error-robust fluorescence in situ hybridization (MERFISH). Within lesion rims, we identified CD8+ T cell niches associated with inflamed microglia displaying an interferon response and upregulated lipid metabolism. To investigate their function, we deleted ATP-binding cassette transporters A1 and G1 (ABCA1/G1) in the microglia of mice with experimental autoimmune encephalomyelitis (EAE), which increased the formation of lipid-storing phagocytes that amplified inflammation. Moreover, pharmacologically targeting sterol metabolism mitigated foam cell formation and inflammatory demyelination in EAE. Thus, our high-resolution map of immune niches in chronic active MS lesions identifies a role for lipid-storing, dysfunctional microglia in persistent neuroinflammation.
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000282602 650_7 $$2Other$$aCD8+ T cells
000282602 650_7 $$2Other$$aCD8+ tissue-resident memory T cells
000282602 650_7 $$2Other$$aglia
000282602 650_7 $$2Other$$alipids
000282602 650_7 $$2Other$$amicroglia
000282602 650_7 $$2Other$$amultiple sclerosis
000282602 650_7 $$2Other$$amyelin
000282602 650_7 $$2Other$$aneuroinflammation
000282602 650_7 $$2Other$$aspatial transcriptomics
000282602 650_7 $$2NLM Chemicals$$aATP Binding Cassette Transporter 1
000282602 650_2 $$2MeSH$$aAnimals
000282602 650_2 $$2MeSH$$aMultiple Sclerosis: immunology
000282602 650_2 $$2MeSH$$aMultiple Sclerosis: genetics
000282602 650_2 $$2MeSH$$aMultiple Sclerosis: pathology
000282602 650_2 $$2MeSH$$aMultiple Sclerosis: metabolism
000282602 650_2 $$2MeSH$$aMice
000282602 650_2 $$2MeSH$$aEncephalomyelitis, Autoimmune, Experimental: immunology
000282602 650_2 $$2MeSH$$aEncephalomyelitis, Autoimmune, Experimental: genetics
000282602 650_2 $$2MeSH$$aEncephalomyelitis, Autoimmune, Experimental: pathology
000282602 650_2 $$2MeSH$$aMicroglia: immunology
000282602 650_2 $$2MeSH$$aMicroglia: metabolism
000282602 650_2 $$2MeSH$$aSingle-Cell Analysis: methods
000282602 650_2 $$2MeSH$$aTranscriptome
000282602 650_2 $$2MeSH$$aInflammation: immunology
000282602 650_2 $$2MeSH$$aInflammation: genetics
000282602 650_2 $$2MeSH$$aGene Expression Profiling
000282602 650_2 $$2MeSH$$aMice, Inbred C57BL
000282602 650_2 $$2MeSH$$aHumans
000282602 650_2 $$2MeSH$$aCD8-Positive T-Lymphocytes: immunology
000282602 650_2 $$2MeSH$$aFemale
000282602 650_2 $$2MeSH$$aATP Binding Cassette Transporter 1: genetics
000282602 650_2 $$2MeSH$$aATP Binding Cassette Transporter 1: metabolism
000282602 650_2 $$2MeSH$$aLipid Metabolism
000282602 650_2 $$2MeSH$$aChronic Disease
000282602 7001_ $$0P:(DE-2719)9002306$$aSpieth, Lena$$b1$$udzne
000282602 7001_ $$0P:(DE-2719)9002890$$aLiu, Lu$$b2$$udzne
000282602 7001_ $$0P:(DE-2719)9001700$$aBerghoff, Stefan$$b3$$udzne
000282602 7001_ $$0P:(DE-HGF)0$$aFranz, Jonas$$b4
000282602 7001_ $$0P:(DE-2719)9002904$$aLiu, Qian$$b5$$udzne
000282602 7001_ $$0P:(DE-2719)9003032$$aWang, Zhen$$b6$$udzne
000282602 7001_ $$0P:(DE-2719)9001975$$aTiwari, Vini$$b7$$udzne
000282602 7001_ $$0P:(DE-2719)9002093$$aVitale, Simona$$b8$$udzne
000282602 7001_ $$aFrerich, Simon$$b9
000282602 7001_ $$0P:(DE-HGF)0$$aFlorensa, Sergi$$b10
000282602 7001_ $$0P:(DE-HGF)0$$aJunker, Niklas$$b11
000282602 7001_ $$0P:(DE-2719)9003174$$aHuber, Ludwig$$b12$$udzne
000282602 7001_ $$aKeller, Marco$$b13
000282602 7001_ $$aMüller, Christoph$$b14
000282602 7001_ $$aBracher, Franz$$b15
000282602 7001_ $$aGe, Xiaoke$$b16
000282602 7001_ $$aRensen, Patrick C N$$b17
000282602 7001_ $$aKooij, Gijs$$b18
000282602 7001_ $$aHosang, Leon$$b19
000282602 7001_ $$aChornyi, Serhii$$b20
000282602 7001_ $$0P:(DE-2719)2000030$$aDichgans, Martin$$b21$$udzne
000282602 7001_ $$0P:(DE-2719)9002754$$aGokce, Ozgun$$b22$$udzne
000282602 7001_ $$aSaher, Gesine$$b23
000282602 7001_ $$aStadelmann, Christine$$b24
000282602 7001_ $$aGiera, Martin$$b25
000282602 7001_ $$0P:(DE-2719)9002589$$aGroh, Janos$$b26$$udzne
000282602 7001_ $$0P:(DE-2719)2811642$$aSimons, Mikael$$b27$$eLast author$$udzne
000282602 773__ $$0PERI:(DE-600)2001966-X$$a10.1016/j.immuni.2025.10.003$$gVol. 58, no. 12, p. 2989 - 3005.e10$$n12$$p2989 - 3005.e10$$tImmunity$$v58$$x1074-7613$$y2025
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