title: Elevated ATG5 expression in autoimmune demyelination and multiple sclerosis.
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.
authors.affiliation: Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California 92037, USA. malireza@scripps.edu
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Alirezaei
authors.forename: Howard S
authors.initials: HS
authors.lastname: Fox
authors.forename: Claudia T
authors.initials: CT
authors.lastname: Flynn
authors.forename: Craig S
authors.initials: CS
authors.lastname: Moore
authors.forename: Andrea L O
authors.initials: AL
authors.lastname: Hebb
authors.forename: Ricardo F
authors.initials: RF
authors.lastname: Frausto
authors.forename: Virender
authors.initials: V
authors.lastname: Bhan
authors.forename: William B
authors.initials: WB
authors.lastname: Kiosses
authors.forename: J Lindsay
authors.initials: JL
authors.lastname: Whitton
authors.forename: George S
authors.initials: GS
authors.lastname: Robertson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Crocker
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000071187:Autophagy-Related Protein 5; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: C502778:ATG5 protein, human; C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger