Cxcl10 enhances blood cells migration in the sub-ventricular zone of mice affected by experimental autoimmune encephalomyelitis

Luca Muzio, Francesca Cavasinni, Cinzia Marinaro, Andrea Bergamaschi, Alessandra Bergami, Cristina Porcheri, Federica Cerri, Giorgia Dina, Angelo Quattrini, Giancarlo Comi, Roberto Furlan, Gianvito Martino

Research output: Contribution to journalArticle

Abstract

The peri-ventricular area of the forebrain constitutes a preferential site of inflammation in multiple sclerosis, and the sub-ventricular zone (SvZ) is functionally altered in its animal model experimental autoimmune encephalomyelitis (EAE). The reasons for this preferential localization are still poorly understood. We show here that, in EAE mice, blood-derived macrophages, T and B cells and microglia (Mg) from the surrounding parenchyma preferentially accumulate within the SvZ, deranging its cytoarchitecture. We found that the chemokine Cxcl10 is constitutively expressed by a subset of cells within the SvZ, constituting a primary chemo-attractant signal for activated T cells. During EAE, T cells and macrophages infiltrating the SvZ in turn secrete pro-inflammatory cytokines such as TNFα and IFNγ capable to induce Mg cells accumulation and SvZ derangement. Accordingly, lentiviral-mediated over-expression of IFNγ or TNFα in the healthy SvZ mimics Mg/microglia recruitment occurring during EAE, while Cxcl10 over-expression in the SvZ is able to increase the frequency of peri-ventricular inflammatory lesions only in EAE mice. Finally, we show, by RT-PCR and in situ hybridization, that Cxcl10 is expressed also in the healthy human SvZ, suggesting a possible molecular parallelism between multiple sclerosis and EAE.

Original languageEnglish
Pages (from-to)268-280
Number of pages13
JournalMolecular and Cellular Neuroscience
Volume43
Issue number3
DOIs
Publication statusPublished - Mar 2010

Keywords

  • Cxcl10
  • EAE
  • Macrophages
  • Neural stem cell niches
  • SvZ

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Cellular and Molecular Neuroscience

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