Identification of naturally occurring fatty acids of the myelin sheath that resolve neuroinflammation.
Sci Transl Med, 2012/6/06;4(137):137ra73.
Ho PP[1], Kanter JL, Johnson AM, Srinagesh HK, Chang EJ, Purdy TM, van Haren K, Wikoff WR, Kind T, Khademi M, Matloff LY, Narayana S, Hur EM, Lindstrom TM, He Z, Fiehn O, Olsson T, Han X, Han MH, Steinman L, Robinson WH
Affiliations
PMID: 22674551DOI: 10.1126/scitranslmed.3003831
Impact factor: 19.319
Abstract
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.
MeSH terms
Animals; Autoantibodies; Blotting, Western; Encephalomyelitis, Autoimmune, Experimental; Fatty Acids; Female; Flow Cytometry; In Situ Nick-End Labeling; Mice; Multiple Sclerosis; Myelin Sheath; Phospholipids
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