Document Detail


Identification of naturally occurring fatty acids of the myelin sheath that resolve neuroinflammation.
MedLine Citation:
PMID:  22674551     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Lipids constitute 70% of the myelin sheath, and autoantibodies against lipids may contribute to the demyelination that characterizes multiple sclerosis (MS). We used lipid antigen microarrays and lipid mass spectrometry to identify bona fide lipid targets of the autoimmune response in MS brain, and an animal model of MS to explore the role of the identified lipids in autoimmune demyelination. We found that autoantibodies in MS target a phosphate group in phosphatidylserine and oxidized phosphatidylcholine derivatives. Administration of these lipids ameliorated experimental autoimmune encephalomyelitis by suppressing activation and inducing apoptosis of autoreactive T cells, effects mediated by the lipids' saturated fatty acid side chains. Thus, phospholipids represent a natural anti-inflammatory class of compounds that have potential as therapeutics for MS.
Authors:
Peggy P Ho; Jennifer L Kanter; Amanda M Johnson; Hrishikesh K Srinagesh; Eun-Ju Chang; Timothy M Purdy; Keith van Haren; William R Wikoff; Tobias Kind; Mohsen Khademi; Laura Y Matloff; Sirisha Narayana; Eun Mi Hur; Tamsin M Lindstrom; Zhigang He; Oliver Fiehn; Tomas Olsson; Xianlin Han; May H Han; Lawrence Steinman; William H Robinson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Science translational medicine     Volume:  4     ISSN:  1946-6242     ISO Abbreviation:  Sci Transl Med     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-07     Completed Date:  2012-10-03     Revised Date:  2014-07-29    
Medline Journal Info:
Nlm Unique ID:  101505086     Medline TA:  Sci Transl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  137ra73     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Autoantibodies / therapeutic use
Blotting, Western
Encephalomyelitis, Autoimmune, Experimental / immunology,  metabolism
Fatty Acids / metabolism*
Female
Flow Cytometry
In Situ Nick-End Labeling
Mice
Multiple Sclerosis / immunology,  therapy
Myelin Sheath / metabolism*
Phospholipids / immunology,  metabolism
Grant Support
ID/Acronym/Agency:
R01 AG031675/AG/NIA NIH HHS; T32 AI007290/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Autoantibodies; 0/Fatty Acids; 0/Phospholipids
Comments/Corrections

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