CNS fibroblasts form a fibrotic scar in response to immune cell infiltration.
Journal
Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
12
12
2019
accepted:
20
11
2020
entrez:
2
2
2021
pubmed:
3
2
2021
medline:
30
3
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33526922
doi: 10.1038/s41593-020-00770-9
pii: 10.1038/s41593-020-00770-9
pmc: PMC7877789
mid: NIHMS1648847
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
234-244Subventions
Organisme : NINDS NIH HHS
ID : R01 NS103844
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS091281
Pays : United States
Organisme : NINDS NIH HHS
ID : P01 NS083513
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS047101
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS034939
Pays : United States
Organisme : NINDS NIH HHS
ID : F31 NS108651
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS097551
Pays : United States
Organisme : NINDS NIH HHS
ID : K08 NS096192
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS119954
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS119615
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007752
Pays : United States
Commentaires et corrections
Type : CommentIn
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