Details

Autor(en) / Beteiligte

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

Titel

Elevated ATG5 expression in autoimmune demyelination and multiple sclerosis

Ist Teil von

• Autophagy, 2009, Vol.5 (2), p.152-158

Ort / Verlag

Taylor & Francis

Erscheinungsjahr

2009

Quelle

Taylor & Francis

Beschreibungen/Notizen

• 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.