Abstract
Omega (ω)–3 long-chain polyunsaturated fatty acids (LCPUFAs) inhibit the production of inflammatory mediators and thereby contribute to the regulation of inflammation. Experimental autoimmune uveitis (EAU) is a well-established animal model of autoimmune retinal inflammation. To investigate the potential effects of dietary intake of ω-3 LCPUFAs on uveitis, we examined the anti-inflammatory properties of these molecules in comparison with ω-6 LCPUFAs in a mouse EAU model. C57BL/6 mice were fed a diet containing ω-3 LCPUFAs or ω-6 LCPUFAs for 2 weeks before as well as after the induction of EAU by subcutaneous injection of a fragment of human interphotoreceptor retinoid-binding protein emulsified with complete Freund’s adjuvant. Both clinical and histological scores for uveitis were smaller for mice fed ω-3 LCPUFAs than for those fed ω-6 LCPUFAs. The concentrations of the T helper 1 (Th1) cytokine interferon-γ and the Th17 cytokine interleukin-17 in intraocular fluid as well as the production of these cytokines by lymph node cells were reduced for mice fed ω-3 LCPUFAs. Furthermore, the amounts of mRNAs for the Th1- and Th17-related transcription factors T-bet and RORγt, respectively, were reduced both in the retina and in lymph node cells of mice fed ω-3 LCPUFAs. Our results thus show that a diet enriched in ω-3 LCPUFAs suppressed uveitis in mice in association with inhibition of Th1 and Th17 cell function.
Highlights
Lipid autacoids have well-established roles in physiology and pathophysiology
We have shown that dietary ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) suppressed intraocular inflammation, as evaluated both clinically and histologically, in mice with Experimental autoimmune uveitis (EAU)
Dietary ω-3 LCPUFAs reduced the concentrations of inflammatory cytokines and chemokines in intraocular fluid of EAU mice as well as attenuated the expression of key transcription factors in retinal T helper 1 (Th1) and Th17 cells
Summary
Lipid autacoids have well-established roles in physiology and pathophysiology. Omega (ω)–3 and ω-6 long-chain polyunsaturated fatty acids (LCPUFAs) are two classes of dietary lipid [1]PLOS ONE | DOI:10.1371/journal.pone.0138241 September 22, 2015Omega-3 Fatty Acids Suppress Autoimmune Uveitis that are highly enriched in the retina [2] and which have opposing physiological effects. Omega (ω)–3 and ω-6 long-chain polyunsaturated fatty acids (LCPUFAs) are two classes of dietary lipid [1]. Ω-3 LCPUFAs have been shown to suppress ocular inflammation in a mouse endotoxininduced uveitis (EIU) model [10] as well as ocular neovascularization in animal models of agerelated macular degeneration [11, 12] or of oxygen-induced retinopathy [3]. The mechanism of such suppression of ocular inflammation by ω-3 LCPUFAs has remained unclear,
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