Identification of naturally occurring fatty acids of the myelin sheath that resolve neuroinflammation

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 SteinmanWilliam H. Robinson

Research output: Contribution to journalArticle

43 Scopus citations

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.

Original languageEnglish (US)
Article number137ra73
JournalScience Translational Medicine
Volume4
Issue number137
DOIs
StatePublished - Jun 6 2012

ASJC Scopus subject areas

  • Medicine(all)

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    Ho, P. P., Kanter, J. L., Johnson, A. M., Srinagesh, H. K., Chang, E. J., Purdy, T. M., Van Haren, K., Wikoff, W. R., Kind, T., Khademi, M., Matloff, L. Y., Narayana, S., Hur, E. M., Lindstrom, T. M., He, Z., Fiehn, O., Olsson, T., Han, X., Han, M. H., ... Robinson, W. H. (2012). Identification of naturally occurring fatty acids of the myelin sheath that resolve neuroinflammation. Science Translational Medicine, 4(137), [137ra73]. https://doi.org/10.1126/scitranslmed.3003831