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

J Biol Chem. 2023 Feb;299(2):102886. doi: 10.1016/j.jbc.2023.102886. Epub 2023 Jan 7.


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 naïve 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.

Keywords: T-cell; cannabinoid; endocannabinoid; experimental autoimmune encephalomyelitis; multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Disease Progression
  • Docosahexaenoic Acids* / metabolism
  • Docosahexaenoic Acids* / pharmacology
  • Encephalomyelitis, Autoimmune, Experimental* / drug therapy
  • Encephalomyelitis, Autoimmune, Experimental* / metabolism
  • Endocannabinoids / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / metabolism
  • Recurrence
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects


  • Docosahexaenoic Acids
  • Endocannabinoids
  • N-docosahexaenoylethanolamide