PubMed

Oral administration of retinoic acid receptor-alpha/beta-specific ligand Am80 suppresses experimental autoimmune uveoretinitis.

Authors

Keino H, Watanabe T, Sato Y, Okada AA.

Journal

Invest Ophthalmol Vis Sci. 2011 Mar 1;52(3):1548-56. doi: 10.1167/iovs.10-5963.

Affiliation

Abstract

PURPOSE: To determine whether synthetic retinoic acid receptor (RAR)-α/β-specific agonist Am80 reduces inflammation in experimental autoimmune uveoretinitis (EAU).

METHODS: Naive CD4(+) T cells were activated with anti-CD3, anti-CD28, and transforming growth factor (TGF)-β, in the presence or absence of Am80. Intracellular expression of forkhead box p3 (Foxp3) and interleukin (IL)-17 in the activated CD4(+) T cells was assessed by flow cytometry. For induction of EAU, C57BL/6 mice were immunized with human interphotoreceptor retinoid binding protein (IRBP) peptide 1 to 20 (IRBP(1-20)). Am80 was administered orally every other day (3 mg/kg/time point) from day 0 to day 21. In vivo primed draining lymph node cells from vehicle-treated or Am80-treated mice were stimulated with IRBP(1-20), and culture supernatant was harvested for assay of interferon (IFN)-γ, IL-6, IL-10, and IL-17. The expression of Foxp3 and IL-6 receptor α in CD4(+) T cells of draining lymph node cells was assessed by a flow cytometer.

RESULTS: Am80 synergized with TGF-β to induce Foxp3(+) T regulatory cells (Treg) and reciprocally inhibited development of IL-17-producing T helper cells (Th17) induced by TGF-β and IL-6. Am80 treatment reduced the severity of EAU clinically, and IFN-γ and IL-17 production was significantly reduced in Am80-treated mice. In addition, the expression of IL-6 receptor α on CD4(+) T cells was downregulated in Am80-treated mice.

CONCLUSIONS: These findings demonstrate that Am80 treatment ameliorates severity of EAU and reduces the Th1/Th17 responses. The synthetic retinoid Am80 appears to be a promising agent for preventing autoimmune uveoretinal inflammation.

PMID

20861477 [PubMed - indexed for MEDLINE]
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