Anti-inflammatory effect of retinoic acid on experimental autoimmune uveoretinitis

Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan.
The British journal of ophthalmology (Impact Factor: 2.98). 12/2009; 94(6):802-7. DOI: 10.1136/bjo.2009.171314
Source: PubMed

ABSTRACT To determine whether an active metabolite of vitamin A, all-trans retinoic acid (ATRA), reduces inflammation in experimental autoimmune uveoretinitis (EAU).
Naive CD4(+) T cells were activated with anti-CD3, anti-CD28 and transforming growth factor (TGF)-beta, in the presence or absence of ATRA. Intracellular expression of transcription factor forkhead box P3 (Foxp3) and interleukin (IL)-17 in the activated CD4(+) T cells was assessed by flow cytometry. C57BL/6 mice were immunised with human interphotoreceptor retinoid binding protein peptide 1-20 (IRBP(1-20)). ATRA was administered intraperitoneally every other day (0.2 mg/mouse per day) from day 0 to day 21. In vivo-primed draining lymph node cells from vehicle-treated or ATRA-treated mice were stimulated with IRBP(1-20) and the culture supernatant fraction was harvested for assay of interferon (IFN)-gamma and IL-17 by ELISA.
ATRA synergised with TGF-beta to induce Foxp3(+) T regulatory cells (Treg) and reciprocally inhibited development of IL-17-producing T helper cells (Th17) induced by TGF-beta and IL-6. ATRA treatment reduced the severity of EAU clinically, and IFN-gamma and IL-17 production were significantly reduced in ATRA-treated mice.
These findings demonstrate that ATRA treatment ameliorates severity of EAU and reduces the Th1/Th17 responses. ATRA may represent a new therapeutic modality for human refractory uveitis.

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    • "These observations prompt the conclusion that αA administration may impact the retina in a more specific fashion where marked elevation of this cytokine (IL17) occurs during early phase of EAU development [25]. This conclusion is supported by observations that IL-17 −/− mice show known reduced inflammation in EAU [27] and the recent report on the amelioration of the severity of EAU by all-trans retinoic acid, which inhibits the emergence of the IL17 producing Th17 cells [28]. In light of this data an investigation into a molecular mechanistic link direct or indirect (via Th17 cells) between αA and IL17 expression will be rewarding. "
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