Fibrotic scar after experimental autoimmune encephalomyelitis inhibits oligodendrocyte differentiation

Stephanie L. Yahn, Jiajun Li, Irene Goo, Han Gao, Roberta Brambilla, Jae K. Lee

Research output: Contribution to journalArticle

Abstract

Remyelination failure is a crucial component of disease progression in the autoimmune demyelinating disease Multiple Sclerosis (MS). The regenerative capacity of oligodendrocyte progenitor cells (OPCs) to replace myelinating oligodendrocytes is likely influenced by many aspects of the lesion environment including inflammatory signaling and extracellular matrix (ECM) deposition. These features of MS lesions are typically attributed to infiltrating leukocytes and reactive astrocytes. Here we demonstrate that fibroblasts also contribute to the inhibitory environment in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Using Col1α1GFP transgenic mice, we show that perivascular fibroblasts are activated in the spinal cord at EAE onset, and infiltrate the parenchyma by the peak of behavioral deficits where they are closely associated with areas of demyelination, myeloid cell accumulation, and ECM deposition. We further show that both fibroblast conditioned media and fibroblast ECM inhibit the differentiation of OPCs into mature oligodendrocytes. Taken together, our results indicate that the fibrotic scar is a major component of EAE pathology that leads to an inhibitory environment for remyelination, thus raising the possibility that anti-fibrotic mechanisms may serve as novel therapeutic targets for MS.

Original languageEnglish (US)
Article number104674
JournalNeurobiology of Disease
Volume134
DOIs
StatePublished - Feb 2020

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Autoimmune Experimental Encephalomyelitis
Oligodendroglia
Multiple Sclerosis
Cicatrix
Fibroblasts
Extracellular Matrix
Demyelinating Diseases
Stem Cells
Myeloid Cells
Conditioned Culture Medium
Astrocytes
Transgenic Mice
Autoimmune Diseases
Disease Progression
Spinal Cord
Leukocytes
Animal Models
Pathology
Therapeutics

Keywords

  • EAE
  • Fibrosis
  • Fibrotic scar
  • MS
  • Myelination
  • OPCs
  • Perivascular fibroblasts

ASJC Scopus subject areas

  • Neurology

Cite this

Fibrotic scar after experimental autoimmune encephalomyelitis inhibits oligodendrocyte differentiation. / Yahn, Stephanie L.; Li, Jiajun; Goo, Irene; Gao, Han; Brambilla, Roberta; Lee, Jae K.

In: Neurobiology of Disease, Vol. 134, 104674, 02.2020.

Research output: Contribution to journalArticle

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