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

• Published in: PloS one 2019-07, Vol.14 (7), p.e0219405-e0219405
• Main Authors: Uchi, Sho-Hei, Yanai, Ryoji, Kobayashi, Masaaki, Hatano, Makoto, Kobayashi, Yuka, Yamashiro, Chiemi, Nagai, Tomohiko, Tokuda, Kazuo, Connor, Kip M, Sonoda, Koh-Hei, Kimura, Kazuhiro
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antigen-presenting cells; Antigen-Presenting Cells - drug effects; Antigen-Presenting Cells - immunology; Antigens; Attenuation; Autoimmune diseases; Autoimmune Diseases - complications; Autoimmune Diseases - drug therapy; Autoimmune Diseases - pathology; B cells; Binding proteins; Biological response modifiers; Biology and Life Sciences; Care and treatment; CD4 antigen; Cell Proliferation; Cytokines; Cytokines - metabolism; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Diabetes; Diet; Disease; Disease Models, Animal; Experimental autoimmune uveitis; Experimental autoimmune uveoretinitis; Fatty acids; Fatty Acids, Omega-3 - pharmacology; Fatty Acids, Omega-3 - therapeutic use; Female; Fish oils; Fractionation; Health aspects; House mouse; Inflammation; Inflammation - complications; Inflammation - drug therapy; Inflammation - pathology; Inflammatory bowel disease; Interferon; Interferon-gamma - metabolism; Interleukin 17; Interleukin-17 - metabolism; Interleukins; Interphotoreceptor retinoid-binding protein; Kinases; Lymphocyte Activation - drug effects; Lymphocyte Culture Test, Mixed; Lymphocytes; Lymphocytes T; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mixed leukocyte reaction; Omega 3 fatty acids; Omega 6 fatty acids; Peptides; Physiological aspects; Polyunsaturated fatty acids; Protein binding; Retinoid-binding protein; Rheumatoid arthritis; Spleen - drug effects; Spleen - pathology; Splenocytes; T cells; Th1 Cells - drug effects; Th17 Cells - drug effects; TNF inhibitors; Tumor necrosis factor-TNF; University graduates; Unsaturated fatty acids; Uveitis; Uveitis - complications; Uveitis - drug therapy; Uveitis - pathology; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0219405

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.