Identification of naturally occurring fatty acids of the myelin sheath that resolve neuroinflammation.
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.
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Peggy P
PP
Ho
Jennifer L
JL
Kanter
Amanda M
AM
Johnson
Hrishikesh K
HK
Srinagesh
Eun-Ju
EJ
Chang
Timothy M
TM
Purdy
Keith
K
van Haren
William R
WR
Wikoff
Tobias
T
Kind
Mohsen
M
Khademi
Laura Y
LY
Matloff
Sirisha
S
Narayana
Eun Mi
EM
Hur
Tamsin M
TM
Lindstrom
Zhigang
Z
He
Oliver
O
Fiehn
Tomas
T
Olsson
Xianlin
X
Han
May H
MH
Han
Lawrence
L
Steinman
William H
WH
Robinson
D000818:Animals; D001323:Autoantibodies / Q000627:therapeutic use; D015153:Blotting, Western; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology / Q000628:therapy; D009186:Myelin Sheath / Q000378:metabolism*; D010743:Phospholipids / Q000276:immunology / Q000378:metabolism
D001323:Autoantibodies; D005227:Fatty Acids; D010743:Phospholipids