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Deletion of astroglial CXCL10 delays clinical onset but does not affect progressive axon loss in a murine autoimmune multiple sclerosis model

Authors
  • Mills Ko, Emily1
  • Ma, Joyce H1
  • Guo, Fuzheng1
  • Miers, Laird1
  • Lee, Eunyoung1, 2
  • Bannerman, Peter1
  • Burns, Travis1
  • Ko, David3
  • Sohn, Jiho1
  • Soulika, Athena M1
  • Pleasure, David1
  • 1 UC Davis School of Medicine and Shriners Hospital, Institute for Pediatric Regenerative Medicine, 2425 Stockton Blvd, Sacramento, CA, 95817, USA , Sacramento (United States)
  • 2 Center for Drug Evaluation, CJ Cheiljedang Pharma, San 522-1, Dukpyungli, Majangmyun, Icheon, Kyunggi, 448130, Korea , Icheon (South Korea)
  • 3 UC Davis, Department of Mechanical and Aerospace Engineering, One Shields Avenue, Davis, CA, 95616, USA , Davis (United States)
Type
Published Article
Journal
Journal of Neuroinflammation
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Jun 12, 2014
Volume
11
Issue
1
Identifiers
DOI: 10.1186/1742-2094-11-105
Source
Springer Nature
Keywords
License
Yellow

Abstract

Multiple sclerosis (MS) is characterized by central nervous system (CNS) inflammation, demyelination, and axonal degeneration. CXCL10 (IP-10), a chemokine for CXCR3+ T cells, is known to regulate T cell differentiation and migration in the periphery, but effects of CXCL10 produced endogenously in the CNS on immune cell trafficking are unknown. We created floxed cxcl10 mice and crossed them with mice carrying an astrocyte-specific Cre transgene (mGFAPcre) to ablate astroglial CXCL10 synthesis. These mice, and littermate controls, were immunized with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG peptide) to induce experimental autoimmune encephalomyelitis (EAE). In comparison to the control mice, spinal cord CXCL10 mRNA and protein were sharply diminished in the mGFAPcre/CXCL10fl/fl EAE mice, confirming that astroglia are chiefly responsible for EAE-induced CNS CXCL10 synthesis. Astroglial CXCL10 deletion did not significantly alter the overall composition of CD4+ lymphocytes and CD11b+ cells in the acutely inflamed CNS, but did diminish accumulation of CD4+ lymphocytes in the spinal cord perivascular spaces. Furthermore, IBA1+ microglia/macrophage accumulation within the lesions was not affected by CXCL10 deletion. Clinical deficits were milder and acute demyelination was substantially reduced in the astroglial CXCL10-deleted EAE mice, but long-term axon loss was equally severe in the two groups. We concluded that astroglial CXCL10 enhances spinal cord perivascular CD4+ lymphocyte accumulation and acute spinal cord demyelination in MOG peptide EAE, but does not play an important role in progressive axon loss in this MS model.

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