Elevated ATG5 expression in autoimmune demyelination and multiple sclerosis.
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.
Alirezaei
Mehrdad
M
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California 92037, USA. malireza@scripps.edu
Fox
Howard S
HS
Flynn
Claudia T
CT
Moore
Craig S
CS
Hebb
Andrea L O
AL
Frausto
Ricardo F
RF
Bhan
Virender
V
Kiosses
William B
WB
Whitton
J Lindsay
JL
Robertson
George S
GS
Crocker
Stephen J
SJ
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
C502778:ATG5 protein, human; C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger