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CNS fibroblasts form a fibrotic scar in response to immune cell infiltration.
Open accessAbstract
Fibrosis is a common pathological response to inflammation in many peripheral tissues and can prevent tissue regeneration and repair. Here, we identified persistent fibrotic scarring in the CNS following immune cell infiltration in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Using lineage tracing and single-cell sequencing in EAE, we determined that the majority of the fibrotic scar is derived from proliferative CNS fibroblasts, not pericytes or infiltrating bone marrow-derived cells. Ablating proliferating fibrotic cells using cell-specific expression of herpes thymidine kinase led to an increase in oligodendrocyte lineage cells within the inflammatory lesions and a reduction in motor disability. We further identified that interferon-gamma pathway genes are enriched in CNS fibrotic cells, and the fibrotic cell-specific deletion of Ifngr1 resulted in reduced fibrotic scarring in EAE. These data delineate a framework for understanding the CNS fibrotic response.
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“For example, recent studies implicate activation of perivascular fibroblasts as a contributing factor to neurodegeneration at early stages of Amyotrophic Lateral Sclerosis,20 and meningeal fibroblasts-induced fibrotic scarring has been highlighted as a potential player in the pathogenesis of multiple sclerosis.21”
From Lipid-siRNA conjugate accesses a perivascular transport mechanism and achieves widespread and durable knockdown in the central nervous system (2024) · cites this paper as [21]
Experimental — accuracy not yet measuredIn the citing paper
“a scRNAseq analysis showed that fibroblasts from EAE lesions upregulate interferon γ (IFNγ) signaling, and conditional deletion of IFN receptor γ from fibroblasts partially blocked fibroblast expansion”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Dorrier et al., 2021
In the citing paper
“Using a Col1a1-GFP mouse line in conjunction with an EAE model, two independent groups identified substantial increases in fibroblasts within spinal cord lesion sites”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Dorrier et al., 2021
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Metadata
- Authors
- Dorrier, C. E., Aran, D., Haenelt, E. A., Sheehy, R. N., Hoi, K. K., Pintarić, L., Chen, Y., Lizama, C. O., Cautivo, K. M., Weiner, G. A., Popko, B., Fancy, S. P. J., Arnold, T. D., & Daneman, R.
- Affiliations
- University of California San Diego (US)
- Technion – Israel Institute of Technology (IL)
- University of California, San Francisco (US)
- Northwestern University (US)
- Corresponding author
- Arnold, Thomas D.
- Daneman, Richard
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2021-02
- Volume
- 24
- Issue
- 2
- Pages
- 234-244
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC7877789
- OpenAlex
- W3128620467
- Cited by
- 199
- References
- 58
- Citations by year
- 2026: 23 · 2025: 35 · 2024: 39 · 2023: 44 · 2022: 33 · 2021: 25
- FWCI
- 23.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NS108651-01A1, NS034939, 5K08NS096192-02)
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (GM007752)
- National Multiple Sclerosis Society
- UCSF Program for Breakthrough Biomedical Science
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- fibrotic scar, multiple sclerosis, experimental autoimmune encephalomyelitis, immune cell infiltration, fibroblast proliferation, meningeal fibrosis, oligodendrocyte lineage, interferon-gamma, IFNGR1, motor impairment, neuroinflammation
- MeSH terms
- Animals, Blood-Brain Barrier, Encephalomyelitis, Autoimmune, Experimental, Fibroblasts, Fibrosis, Oligodendroglia, Spinal Cord, Neutrophil Infiltration, Mice
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