Dendritic cells mediate the anti-inflammatory action of omega-3 long-chain polyunsaturated fatty acids in experimental autoimmune uveitis

Abstract

We previously showed that dietary omega (ω)–3 long-chain polyunsaturated fatty acids (LCPUFAs) suppress inflammation in mice with experimental autoimmune uveitis (EAU). We have now investigated the role of antigen presenting cells (APCs) in this action of ω-3 LCPUFAs. C57BL/6 mice were fed a diet supplemented with ω-3 or ω-6 LCPUFAs for 2 weeks, after which splenocytes were isolated from the mice and cocultured with CD4 + T cells isolated from mice with EAU induced by injection of a human interphotoreceptor retinoid-binding protein peptide together with complete Freund’s adjuvant. The proliferation of and production of interferon-γ and interleukin-17 by T cells from EAU mice in vitro were attenuated in the presence of splenocytes from ω-3 LCPUFA–fed mice as compared with those from mice fed ω-6 LCPUFAs. Splenocyte fractionation by magnetic-activated cell sorting revealed that, among APCs, dendritic cells (DCs) were the target of ω-3 LCPUFAs. Adoptive transfer of DCs from mice fed ω-3 LCPUFAs attenuated disease progression in EAU mice as well as the production of pro-inflammatory cytokines by T cells isolated from these latter animals. The proliferation of T cells from control Balb/c mice was also attenuated in the presence of DCs from ω-3 LCPUFA–fed mice as compared with those from ω-6 LCPUFA–fed mice. Furthermore, T cell proliferation in such a mixed lymphocyte reaction was inhibited by prior exposure of DCs from mice fed an ω-6 LCPUFA diet to ω-3 LCPUFAs in vitro. Our results thus suggest that DCs mediate the anti-inflammatory action of dietary ω-3 LCPUFAs in EAU.

The Influence of Dietary Fatty Acids on Immune Responses

“…Observed effect is mediated by reduced Th1-inducing (CD11c + CD11b − CD8α + ) lymphoid DCs and increased tolerogenic, myeloid (CD11c + CD11b + CD8α − ) DCs subpopulations [112,113]. In vivo anti-inflammatory actions of dietary n-3 PUFAs are also shown as the inhibition of T cell proliferation and the production of IFN-γ and IL-17 [114].…”

Mediterranean Diet: Lipids, Inflammation, and Malaria Infection

“…Transfer of dendritic cells from mice fed omega-3 long-chain PUFA diet to mice with EAU decreased the T cell proliferation and the production of IFN-γ and IL-17 by T cells, mitigating the disease development. Splenocytes were isolated from the mice and cocultured with CD4 + T cells isolated from mice with EAU [ 137 ]. Omega-3 long-chain PUFA seem to have a molecular target in T cells, the T-bet and RORγt, Th1- and Th17-related transcription factors, respectively.…”

New Insights Into Immunological Therapy for Retinal Disorders

“…In a previous study, conducted by the authors of the present review, we found that mouse spleen-derived DCs mediate the anti-inflammatory action of dietary ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) in EAU (76). Histological analysis at 17 days after disease induction revealed retinal folds and immune cell infiltration in the eyes of EAU mice that received DCs from ω-6 LCPUFA-fed mice, and showed that such changes were markedly suppressed in EAU mice that received DCs from ω-3 LCPUFA-fed mice ( Figure 1A) (77). Furthermore, DCs exposed to ω-3 LCPUFAs in vivo or in vitro suppressed T cell proliferation.…”

“…* P < 0.05, *** P < 0.001; NS, not significant vs. the corresponding value for the ω-6 LCPUFA diet (i.e., Sidak's multiple comparison test). The figure is reproduced from ( 77 ) with permission.…”