Docosahexaenoic acid prevents dendritic cell maturation, inhibits antigen-specific Th1/Th17 differentiation and suppresses experimental autoimmune encephalomyelitis.
Docosahexaenoic acid (DHA), the most abundant essential n-3 polyunsaturated fatty acid in the CNS, emerged recently together with eicosapentaenoic acid (EPA) and DHA/EPA metabolic derivatives as a major player in the resolution of inflammation. Protective anti-inflammatory effects of DHA were reported in clinical studies and animal models of colitis, sepsis, and stroke. Here we report for the first time a beneficial effect of dietary n-3 fatty acids in experimental autoimmune encephalomyelitis (EAE), a model for human multiple sclerosis. In the present study we investigated the effects of DHA on the function of bone marrow-derived dendritic cells (DC) in CD4(+) T cell stimulation and differentiation. Pretreatment of DC with DHA prevented LPS-induced DC maturation, maintaining an immature phenotype characterized by low expression of costimulatory molecules and lack of proinflammatory cytokine production (IL-12p70, IL-6, and IL-23). DHA-treated DC were poor stimulators of antigen-specific T cells in terms of proliferation and Th1/Th17 differentiation. This was associated with an increase in p27(kip1), a cell cycle arresting agent, and with decreases in Tbet, GATA-3, and RORγt, master transcription factors for Th1, Th2, and Th17. In contrast, T cells co-cultured with DC-DHA express higher levels of TGFβ and Foxp3, without exhibiting a functional Treg phenotype. Similar to the in vitro results, the beneficial effect of DHA in EAE was associated with reduced numbers of IFNγ- and IL-17-producing CD4(+) T cells in both spleen and CNS.
Kong
Weimin
W
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Yen
Jui-Hung
JH
Ganea
Doina
D
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000187:drug effects* / Q000502:physiology; D058504:Th17 Cells / Q000187:drug effects* / Q000502:physiology
D016207:Cytokines; D004281:Docosahexaenoic Acids