Docosahexaenoic acid ameliorates autoimmune inflammation by activating GPR120 signaling pathway in dendritic cells.

Although the phenomenon that omega-3 polyunsaturated fatty acids (n-3 PUFAs) shows to have a beneficial effect in patients suffering from multiple sclerosis (MS) and other autoimmune diseases has been empirically well-documented, the molecular mechanisms that underline the anti-inflammatory effects of n-3 PUFAs are yet to be understood. In experimental autoimmune encephalomyelitis (EAE), a model for MS, we show that one of the underlying mechanisms by which dietary docosahexaenoic acid (DHA) exerts its anti-inflammatory effect is regulating the functional activities of dendritic cells (DCs). In DHA-treated EAE mice, DCs acquire a regulatory phenotype characterized by low expression of co-stimulatory molecules, decreased production of pro-inflammatory cytokines, and enhanced capability of regulatory T-cell induction. The effect of DHA on DCs is mediated by the lipid-sensing receptor, G protein-coupled receptor 120 (GPR120). A GPR120-specific small-molecule agonist could ameliorate the autoimmune inflammation by regulating DCs, while silencing GPR120 in DCs strongly increased the immunogenicity of DCs. Stimulation of GPR120 induces suppressor of cytokine signaling 3 (SOCS3) expression and down-regulates signal transducer and activator of transcription 3 (STAT3) phosphorylation, explaining the molecular mechanism for regulatory DC induction.