Research ArticleMultiple Sclerosis

Identification of Naturally Occurring Fatty Acids of the Myelin Sheath That Resolve Neuroinflammation

Science Translational Medicine  06 Jun 2012:
Vol. 4, Issue 137, pp. 137ra73
DOI: 10.1126/scitranslmed.3003831

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Eliminating Excess

In tough economic times, businesses trim the fat by cutting superfluous spending. The immune system also has ways to regulate excess, such as feedback mechanisms that prevent autoimmunity. In patients with multiple sclerosis (MS), these protective mechanisms fail: The immune system attacks peripheral nerves, resulting in demyelination and a decrease in the ability of axons to carry physiological signals. Researchers have identified autoantibodies to many of the lipids that make up the myelin sheath of nerve cells, and these target lipids are believed to serve as pathogenic antigens for autoimmune encephalomyelitis—an inflammation of the brain and spinal cord seen in MS patients. However, new work by Ho et al. shows that some fat shouldn’t be trimmed; indeed, certain fatty acids of the myelin sheath actually serve to resolve neuroinflammation in a therapeutic mouse model of MS, experimental autoimmune encephalomyelitis (EAE).

With lipid antigen microarrays and mass spectrometry, the authors identified targets of the autoimmune response in the brains of patients with MS and then used these lipid antigens to immunize mice with clinical EAE symptoms. Some of the phospholipids tested suppressed activation of and induced apoptosis in autoreactive T cells, ameliorating disease in the EAE mice, an effect that was mediated by the lipids’ fatty acid side chains. These data suggest that some phospholipids are natural anti-inflammatory compounds composed of fatty acids that trim the fat—in this case, excessive behavior by the immune system.