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Hypomethylating agent 5-aza-2'-deoxycytidine (DAC) ameliorates multiple sclerosis in mouse models

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  • Katia Mangano
  • Paolo Fagone
  • Klaus Bendtzen
  • Pier Luigi Meroni
  • Cinzia Quattrocchi
  • Santa Mammana
  • Michelino Di Rosa
  • Lucia Malaguarnera
  • Marinella Coco
  • Gaetano Magro
  • Roberto Di Marco
  • Ferdinando Nicoletti
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Increasing evidence supports the role of epigenetics in the development of autoimmune disorders and the possibility of using epigenetic modifying drugs in the context of MS has not yet been investigated. We have explored the effect of the hypomethylating agent 5-aza-2'-deoxycytidine (DAC) in two murine models of experimental allergic encephalomyelitis (EAE). DAC treatment was associated with a significant amelioration of the clinical and histological hallmarks of EAE in both models. These effects were observed both in prophylactic and therapeutic regimens. The milder course of the disease was associated with a reduction in the number of spinal cord infiltrating lymphocytes and amelioration of the histopathological signs associated with EAE. In addition, increased transcript levels of anti-inflammatory cytokines and decreased mRNA expression of pro-inflammatory mediators were also observed. Finally, DAC treatment increased the percentage of circulating regulatory T cells by inducing Foxp3 expression via demethylation of a CpG island in Foxp3.

Original languageEnglish
JournalJournal of Cellular Physiology
Volume229
Issue number12
Pages (from-to)1918-25
Number of pages8
ISSN0021-9541
DOIs
Publication statusPublished - Dec 2014

    Research areas

  • Animals, Anti-Inflammatory Agents, Azacitidine, Cytokines, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Mice, Multiple Sclerosis, T-Lymphocytes, Regulatory

ID: 44982981