Anti-inflammatory effect of retinoic acid on experimental autoimmune uveoretinitis
- 1Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan
- 2Division of Radioisotope Research, Kyorin University School of Medicine, Tokyo, Japan
- Correspondence to Dr Hiroshi Keino, Department of Ophthalmology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan;
- Accepted 4 November 2009
- Published Online First 3 December 2009
Aims To determine whether an active metabolite of vitamin A, all-trans retinoic acid (ATRA), 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 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 (IRBP1–20). 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 IRBP1–20 and the culture supernatant fraction was harvested for assay of interferon (IFN)-γ and IL-17 by ELISA.
Results ATRA synergised 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. ATRA treatment reduced the severity of EAU clinically, and IFN-γ and IL-17 production were significantly reduced in ATRA-treated mice.
Conclusion 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.
- Experimental autoimmune uveoretinitis
- all-trans retinoic acid
- treatment medical
- experimental and animal models
Funding This work was supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.
Competing interests None.
Ethics approval Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.