Abstract
Purpose: :
Experimental autoimmune uveitis (EAU) is a T cell mediated inflammatory disease that shares essential pathological features with human uveitis and serves as a mouse model of posterior uveitis. Th17 and Th1 cells have been implicated in the etiology of uveitis and suppressing the expansion of these CD4+ T cell subsets during uveitis may be therapeutically beneficial. Resveratrol is an antioxidant polyphenols contained in red wine and grape skin and has been shown to possess anti-inflammatory properties. In this study, we investigated whether Resveratrol might inhibit the expansion of uveitogenic T cells and ameliorate EAU.
Methods: :
The naïve CD4 T cells from C57BL/6 mice were isolated and cultured under Th1 or Th17 polarization condition in the presence or absence of Resveratrol. Cellular proliferation/expansion was determined by the antigen-induced CD154 expression assay, 3H-thymidine incorporation or CFSE labeling assay. Gene expression was analyzed by RT-PCR and quantified by qPCR. Intracellular cytokine expression was detected by FACS analysis and effects of Resveratrol on cell survival was determined by Annexin-V staining assay. EAU was induced by adoptive transfer of IRBP-specific pathogenic T cells and effects of Resveratrol on development and severity of EAU was monitored by fundoscopy or histopathology.
Results: :
Resveratrol suppressed the differentiation of Th17 and Th1 cells and inhibited the expansion of uveitogenic Th17 cells during EAU. Resveratrol inhibited adoptive transfer of uveitis to syngeneic mice.
Conclusions: :
Resveratrol could potentially be a safe and effective drug for treating uveitis and other autoimmune disease.
Keywords: autoimmune disease • immunomodulation/immunoregulation • inflammation