Elevated ATG5 expression in autoimmune demyelination and multiple sclerosis

Mehrdad Alirezaei, Howard S. Fox, Claudia T. Flynn, Craig S. Moore, Andrea L.O. Hebb, Ricardo F. Frausto, Virender Bhan, William B. Kiosses, J. Lindsay Whitton, George S. Robertson, Stephen J. Crocker

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

Multiple sclerosis (MS) is an inflammatory central nervous system (CNS) disorder characterized by T cell-mediated demyelination. In MS, prolonged T cell survival and increased T cell proliferation have been linked to disease relapse and progression. Recently, the autophagy-related gene 5 (Atg5) has been shown to modulate T cell survival. In this study, we examined the expression of Atg5 using both a mouse model of autoimmune demyelination as well as blood and brain tissues from MS cases. Quantitative real-time PCR analysis of RNA isolated from blood samples of experimental autoimmune encephalomyelitis (EAE) mice revealed a strong correlation between Atg5 expression and clinical disability. Analysis of protein extracted from these cells confirmed both upregulation and post-translational modification of Atg5, the latter of which was positively correlated with EAE severity. Analysis of RNA extracted from T cells isolated by negative selection indicated that Atg5 expression was significantly elevated in individuals with active relapsing-remitting MS compared to non-diseased controls. Brain tissue sections from relapsing-remitting MS cases examined by immunofluorescent histochemistry suggested that encephalitogenic T cells are a source of Atg5 expression in MS brain samples. Together these data suggest that increased T cell expression of Atg5 may contribute to inflammatory demyelination in MS.

Original languageEnglish (US)
Pages (from-to)152-158
Number of pages7
JournalAutophagy
Volume5
Issue number2
DOIs
StatePublished - Feb 16 2009

Keywords

  • Apoptosis
  • Atg5
  • Autoimmune
  • Autophagy
  • CNS
  • EAE
  • Encephalomyelitis
  • Multiple sclerosis
  • Neuroinflammation
  • T cell

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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