@article{2406229b43de48baaf507856c3f84c52,
title = "CNS fibroblasts form a fibrotic scar in response to immune cell infiltration",
abstract = "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.",
author = "Dorrier, {Cayce E.} and Dvir Aran and Haenelt, {Ezekiel A.} and Sheehy, {Ryan N.} and Hoi, {Kimberly K.} and Lucija Pintari{\'c} and Yanan Chen and Lizama, {Carlos O.} and Cautivo, {Kelly M.} and Weiner, {Geoffrey A.} and Brian Popko and Fancy, {Stephen P.J.} and Arnold, {Thomas D.} and Richard Daneman",
note = "Funding Information: We thank K. Jepsen and the UCSD Institute of Genomic Medicine Genomics center, T. Lambardo and the UCSD Veterans Hospital Flow Cytometry Core, Y. Jones and the CMM UCSD Electron Microscopy Core and J. Santini and M. Erb at the UCSD Microscopy Core. We thank D. Brenner (UCSD Health Sciences) for kindly supplying the Col1a1-GFP mice. R.D. is funded by National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) awards (R01 NS091281, R01 NS103844), a National Multiple Sclerosis Society grant and the UCSF Program for Breakthrough Biomedical Science. C.E.D. is funded by the UCSD Graduate Training Program in Cellular and Molecular Pharmacology through an institutional training grant from the National Institute of General Medical Sciences (T32 GM007752) and an NIH/NINDS award (F31 NS108651). R.D. and T.A. are funded by NIH/NINDS R01 NS119615. T.A. is funded by NIH/NINDS grant no. 5K08NS096192. B.P. is funded by NIH/NINDS grant no. R01 NS034939. The UCSD Microscopy Core is funded by NINDS grant no. NS047101. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2021",
month = feb,
doi = "10.1038/s41593-020-00770-9",
language = "English (US)",
volume = "24",
pages = "234--244",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "2",
}