The aim of this study is to investigate the effect of resveratrol on Th17 allo-immune responses under tacrolimus (Tac)-based immune suppression. First, we investigated the suppressive effect of resveratrolon T cell proliferation or Th17 associated cytokine level upon T-cell specific stimulation. Second, we determined the protective effect of resveratrol on the inflammation of human primary tubular epithelial cells (HPRTEpiC) induced by IL-17 or activated T cells under Th17 differentiated condition and also investigated the suppressive effect on the proliferation of T cells after co-culture with HPRTEpiC. Lastly, we investigated the pathway of the protective action of resveratrol on T cell or HPRTEpiC. In T cell experiment using PBMCs isolated from healthy volunteers, Tac suppressed Th1, Th2 and regulatory T cells in a concentration-dependent manner, but it did not suppress Th17 cells even at high concentrationIn contrast, addition of resveratrol significantly suppressed Th17 proliferation, and also significantly decrease Th17 associated cytokine level and also mRNA expression. Next, treatment with IL-17 or co-culture with activated T cells significantly induced secretion of IL-6 and IL-8 from HPRTEpiC, and, addition of resveratrol to those conditions significantly reduces those cytokines. Third, T cell showed significantly proliferation after co-culture with HPRTEpiC, but addition of resveratrol significantly suppressed it. Those protective effects of resveratrol were mediated by the augmentation of AMPK and reciprocal suppression of mTOR both in T cells and HPRTEpiC. The results of this study suggests that addition of resveratrol to Tac is beneficial in terms of the effective regulation of Th17 alloimmune responses; hence it could be proposed as strategy to compensate immune suppressive effect of tacrolimus.

CITATION INFORMATION: Chung B, Doh K, Min J.-W, Kim K, Kim B.-M, Cho M.-L, Yang C. Resveratrol Effectively Suppress Th17 Associated Allo-Immune Responses by the Modulation of AMPK/mTOR Pathway. Am J Transplant. 2016;16 (suppl 3).

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