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 Steinman & 1 others William H. Robinson

Research output: Contribution to journalArticle

41 Citations (Scopus)

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

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Myelin Sheath
Fatty Acids
Lipids
Multiple Sclerosis
Demyelinating Diseases
Autoantibodies
Autoimmune Experimental Encephalomyelitis
Phosphatidylserines
Phosphatidylcholines
Autoimmunity
Mass Spectrometry
Phospholipids
Anti-Inflammatory Agents
Animal Models
Phosphates
Apoptosis
T-Lymphocytes
Antigens
Brain

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ho, P. P., Kanter, J. L., Johnson, A. M., Srinagesh, H. K., Chang, E. J., Purdy, T. M., ... 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

Identification of naturally occurring fatty acids of the myelin sheath that resolve neuroinflammation. / Ho, Peggy P.; Kanter, Jennifer L.; Johnson, Amanda M.; Srinagesh, Hrishikesh K.; Chang, Eun Ju; Purdy, Timothy M.; Van Haren, Keith; Wikoff, William R.; Kind, Tobias; Khademi, Mohsen; Matloff, Laura Y.; Narayana, Sirisha; Hur, Eun Mi; Lindstrom, Tamsin M.; He, Zhigang; Fiehn, Oliver; Olsson, Tomas; Han, Xianlin; Han, May H.; Steinman, Lawrence; Robinson, William H.

In: Science Translational Medicine, Vol. 4, No. 137, 137ra73, 06.06.2012.

Research output: Contribution to journalArticle

Ho, PP, 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 2012, 'Identification of naturally occurring fatty acids of the myelin sheath that resolve neuroinflammation', Science Translational Medicine, vol. 4, no. 137, 137ra73. https://doi.org/10.1126/scitranslmed.3003831
Ho, Peggy P. ; Kanter, Jennifer L. ; Johnson, Amanda M. ; Srinagesh, Hrishikesh K. ; Chang, Eun Ju ; Purdy, Timothy M. ; Van Haren, Keith ; Wikoff, William R. ; Kind, Tobias ; Khademi, Mohsen ; Matloff, Laura Y. ; Narayana, Sirisha ; Hur, Eun Mi ; Lindstrom, Tamsin M. ; He, Zhigang ; Fiehn, Oliver ; Olsson, Tomas ; Han, Xianlin ; Han, May H. ; Steinman, Lawrence ; Robinson, William H. / Identification of naturally occurring fatty acids of the myelin sheath that resolve neuroinflammation. In: Science Translational Medicine. 2012 ; Vol. 4, No. 137.
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