Role of omega-3 endocannabinoids in the modulation of T-cell activity in a multiple sclerosis experimental autoimmune encephalomyelitis (EAE) model

Epidemiological studies show that omega-3 fatty acid consumption is associated with improved conditions in neurodegenerative diseases such as multiple sclerosis (MS). However, the mechanism of this association is not well understood. Emerging evidence suggests that parent molecules such as docosahexaenoic acid are converted into downstream metabolites that are capable of directly modulating immune responses. In vitro, we found that docosahexaenoyl ethanolamide (DHEA), another dietary component and its epoxide metabolite, reduced the polarization of naive T-cells toward proinflammatory Th1 and Th17 phenotypes. Furthermore, we identified that DHEA and related endocannabinoids are changing during the disease progression in mice undergoing relapse-remitting experimental autoimmune encephalomyelitis (RR-EAE). In addition, daily administration of DHEA to mice delayed the onset of disease, the rate of relapse, and the severity of clinical scores at relapse in RR-EAE, an animal model of MS. Collectively, these data indicate that DHEA and their downstream metabolites reduce the disease severity in the RR-EAE model of MS and can be potential dietary adjuvants to existing MS therapeutics.

Automated summary

Epidemiological studies have shown a link between omega-3 fatty acid consumption and improved conditions in neurodegenerative diseases like multiple sclerosis (MS), but the underlying mechanism is not well understood. Recent evidence suggests that these fatty acids are converted into metabolites that directly affect immune responses. In experiments, the metabolite docosahexaenoyl ethanolamide (DHEA) was found to reduce inflammatory T-cell polarization. Additionally, DHEA and related endocannabinoids were found to change during disease progression in a mouse model of MS. Administering DHEA to mice delayed disease onset, reduced relapse rates, and improved clinical scores, indicating its potential as a dietary adjuvant for MS treatment.