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@ARTICLE{Feng:282602,
      author       = {Feng, Ruoqing and Spieth, Lena and Liu, Lu and Berghoff,
                      Stefan and Franz, Jonas and Liu, Qian and Wang, Zhen and
                      Tiwari, Vini and Vitale, Simona and Frerich, Simon and
                      Florensa, Sergi and Junker, Niklas and Huber, Ludwig and
                      Keller, Marco and Müller, Christoph and Bracher, Franz and
                      Ge, Xiaoke and Rensen, Patrick C N and Kooij, Gijs and
                      Hosang, Leon and Chornyi, Serhii and Dichgans, Martin and
                      Gokce, Ozgun and Saher, Gesine and Stadelmann, Christine and
                      Giera, Martin and Groh, Janos and Simons, Mikael},
      title        = {{S}ingle-cell spatial transcriptomic profiling defines a
                      pathogenic inflammatory niche in chronic active multiple
                      sclerosis lesions.},
      journal      = {Immunity},
      volume       = {58},
      number       = {12},
      issn         = {1074-7613},
      address      = {[Cambridge, Mass.]},
      publisher    = {Cell Press},
      reportid     = {DZNE-2025-01360},
      pages        = {2989 - 3005.e10},
      year         = {2025},
      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.},
      keywords     = {Animals / Multiple Sclerosis: immunology / Multiple
                      Sclerosis: genetics / Multiple Sclerosis: pathology /
                      Multiple Sclerosis: metabolism / Mice / Encephalomyelitis,
                      Autoimmune, Experimental: immunology / Encephalomyelitis,
                      Autoimmune, Experimental: genetics / Encephalomyelitis,
                      Autoimmune, Experimental: pathology / Microglia: immunology
                      / Microglia: metabolism / Single-Cell Analysis: methods /
                      Transcriptome / Inflammation: immunology / Inflammation:
                      genetics / Gene Expression Profiling / Mice, Inbred C57BL /
                      Humans / CD8-Positive T-Lymphocytes: immunology / Female /
                      ATP Binding Cassette Transporter 1: genetics / ATP Binding
                      Cassette Transporter 1: metabolism / Lipid Metabolism /
                      Chronic Disease / CD8+ T cells (Other) / CD8+
                      tissue-resident memory T cells (Other) / glia (Other) /
                      lipids (Other) / microglia (Other) / multiple sclerosis
                      (Other) / myelin (Other) / neuroinflammation (Other) /
                      spatial transcriptomics (Other) / ATP Binding Cassette
                      Transporter 1 (NLM Chemicals)},
      cin          = {AG Simons / AG Latz / AG Dichgans / AG Gokce},
      ddc          = {610},
      cid          = {I:(DE-2719)1110008 / I:(DE-2719)1013024 /
                      I:(DE-2719)5000022 / I:(DE-2719)1013041},
      pnm          = {351 - Brain Function (POF4-351) / 353 - Clinical and Health
                      Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-351 / G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41167189},
      doi          = {10.1016/j.immuni.2025.10.003},
      url          = {https://pub.dzne.de/record/282602},
}