Effects of resveratrol on Th17 cell-related immune responses under tacrolimus-based immunosuppression

Abstract

Background We previously reported that tacrolimus (Tac) does not decrease T helper 17 cells (Th17) response in kidney transplantation. In this study, we evaluated whether Resveratrol (Resv) has immunosuppressive effects by decreasing Th17 responses in Tac-based immunosuppression. Methods We investigated the effects of Resv under Tac-treatment conditions, on CD4 + T cell differentiation to Th17 cells in peripheral blood mononuclear cells (PBMCs), and proliferation of CD4 + T cells co-cultured with human renal proximal tubular epithelial cells (HRPTEpiCs). The effects of Resv on Th17 cells were tested in the murine skin transplant model. Results In PBMCs, Tac did not but combination of Tac and Resv further suppressed Th17 immune response. In the co-culture study, combination of Resv to Tac significantly decreased HRPTEpiC-induced T cell proliferation compared to Tac alone. Resv treatment in the Jurkat cell induced the expression of AMP-activated protein kinase and suppressed the expression of mammalian target of rapamycin (mTOR), suggesting blocking Th17 pathway by Resv. In the murine skin transplant model, combination of Resv to Tac significantly prolonged skin graft survival accompanied by the suppression of Th17 cells, compared to either the Tac-alone or control groups. Conclusion The results of our study suggest that Resv provides additional immunosuppressive effects to Tac by suppressing effector CD4 + T cells, especially Th17 cells, in the transplantation setting .

Role of Resveratrol in Regulating Cutaneous Functions

“…Inhibition of allergic contact dermatitis by resveratrol could be attributable to the downregulation of interferon regulatory factor 1/ STAT1 signaling pathway and inhibition of phosphorylation of MAPK/p38 and/or phospholipase Cc [113,116,198]. Moreover, resveratrol inhibited proliferation and differentiation of CD+ T cells and proliferation of 17 T cells via upregulation of phosphorylated MAPK and downregulation of phosphorylated mammalian target of rapamycin (p-mTOR) in Jurkat cells [199]. Furthermore, resveratrol-induced inhibition of TNFα-induced cytokine production in fibroblasts is via activation of SIRT1 because knockdown of SIRT1 abolishes the inhibitory effect resveratrol on inflammation [200].…”

Botanical Medicine and Phytochemicals in Healthy Aging and Longevity—Part 1

“…Application of resveratrol resulted in reduced phosphorylation of mTOR in a dose-dependent manner. 67 This study provides an important reminder that the mTOR pathway plays a key role in T cell differentiation, and therefore in the immune response.…”

Resveratrol promotes mammary cell proliferation and antioxidation capacity during pregnancy and lactation in mice

“…Th17 cells mainly secrete IL‐22, and resveratrol can reduce IL‐22 levels through Th17 cells (Doh et al . 2019). Previous study has shown that resveratrol upregulates JNK signalling pathway and reduces cytokine‐induced hepatocyte iNOS (Kimbrough et al .…”