Transcriptional dysregulation of Interferome in experimental and human Multiple Sclerosis

Sundararajan Srinivasan, Martina Severa, Fabiana Rizzo, Ramesh Menon, Elena Brini, Rosella Mechelli, Vittorio Martinelli, Paul Hertzog, Marco Salvetti, Roberto Furlan, Gianvito Martino, Giancarlo Comi, Eliana M. Coccia, Cinthia Farina (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)
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Recent evidence indicates that single multiple sclerosis (MS) susceptibility genes involved in interferon (IFN) signaling display altered transcript levels in peripheral blood of untreated MS subjects, suggesting that responsiveness to endogenous IFN is dysregulated during neuroinflammation. To prove this hypothesis we exploited the systematic collection of IFN regulated genes (IRG) provided by the Interferome database and mapped Interferome changes in experimental and human MS. Indeed, central nervous system tissue and encephalitogenic CD4 T cells during experimental autoimmune encephalomyelitis were characterized by massive changes in Interferome transcription. Further, the analysis of almost 500 human blood transcriptomes showed that (i) several IRG changed expression at distinct MS stages with a core of 21 transcripts concordantly dysregulated in all MS forms compared with healthy subjects; (ii) 100 differentially expressed IRG were validated in independent case-control cohorts; and (iii) 53 out of 100 dysregulated IRG were targeted by IFN-beta treatment in vivo. Finally, ex vivo and in vitro experiments established that IFN-beta administration modulated expression of two IRG, ARRB1 and CHP1, in immune cells. Our study confirms the impairment of Interferome in experimental and human MS, and describes IRG signatures at distinct disease stages which can represent novel therapeutic targets in MS.

Original languageEnglish
Article number8981
Number of pages9
JournalScientific Reports
Publication statusPublished - 21 Aug 2017


  • Adult
  • Aged
  • Animals
  • Blood Cells/immunology
  • CD4-Positive T-Lymphocytes/immunology
  • Case-Control Studies
  • Central Nervous System/pathology
  • Encephalomyelitis, Autoimmune, Experimental/pathology
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunologic Factors/biosynthesis
  • Interferons/biosynthesis
  • Male
  • Mice, Inbred C57BL
  • Middle Aged
  • Multiple Sclerosis/pathology
  • Young Adult

ASJC Scopus subject areas

  • General


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