CNS fibroblasts form a fibrotic scar in response to immune cell infiltration

Autor: Lucija Pintarić, Ezekiel A. Haenelt, Carlos Lizama, Ryan N. Sheehy, Cayce E. Dorrier, Kelly M. Cautivo, Stephen P.J. Fancy, Yanan Chen, Dvir Aran, Richard Daneman, Geoffrey Weiner, Brian Popko, Thomas D. Arnold, Kimberly K. Hoi
Rok vydání: 2019
Předmět:
0301 basic medicine
Pathology
medicine.medical_specialty
Multiple Sclerosis
Encephalomyelitis
Autoimmune
Experimental
1.1 Normal biological development and functioning
Encephalomyelitis
Inflammation
Neurodegenerative
Autoimmune Disease
Experimental
03 medical and health sciences
Mice
0302 clinical medicine
Fibrosis
medicine
2.1 Biological and endogenous factors
Psychology
Animals
Neurology & Neurosurgery
business.industry
Inflammatory and immune system
General Neuroscience
Multiple sclerosis
Experimental autoimmune encephalomyelitis
Neurosciences
Fibroblasts
Stem Cell Research
medicine.disease
Oligodendrocyte
Brain Disorders
Oligodendroglia
030104 developmental biology
Neuroimmunology
medicine.anatomical_structure
Neutrophil Infiltration
Spinal Cord
Blood-Brain Barrier
Experimental pathology
Stem Cell Research - Nonembryonic - Non-Human
Cognitive Sciences
medicine.symptom
business
Neuroscience
030217 neurology & neurosurgery
Autoimmune
Zdroj: Nature neuroscience, vol 24, iss 2
ISSN: 1546-1726
Popis: 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.
Databáze: OpenAIRE
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