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.
Highlights
Uveitis is a sight-threatening intraocular inflammatory disease
To investigate the mechanism underlying the anti-inflammatory action of dietary ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) in experimental autoimmune uveitis (EAU), we isolated antigen presenting cells (APCs) from the spleen of mice fed for 14 days with a diet supplemented either with these fatty acids or with ω-6 LCPUFAs as a control (Fig 1A)
We investigated which type of APC from ω-3 LCPUFA–fed mice is responsible for suppression of the proliferation of and cytokine production by T cells from EAU mice
Summary
Uveitis is a sight-threatening intraocular inflammatory disease. The main treatment for noninfectious uveitis is topical or systemic corticosteroid administration. Long-term corticosteroid treatment is associated with adverse effects such as glaucoma, cataracts, and systemic complications including diabetes, infection, psychological disorders, hypertension, obesity, and osteoporosis [2, 3]. More specific therapies, including the administration of TNF blockers, have recently been introduced for uveitis treatment. Such agents are not necessarily as effective as corticosteroids, not all patients respond to them, and they are expensive and not devoid of side effects. There is a need for new safe and effective treatments for patients with noninfectious uveitis
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