Convergent Research Consortium for Immunologic disease, St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.
Transplant research center, St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.
BMC Complement Altern Med. 2019 Mar 4;19(1):54. doi: 10.1186/s12906-019-2464-1.
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.
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.
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.
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.
我们之前报道过他克莫司（Tac）不会降低肾移植中的辅助性 T 细胞 17 型（Th17）反应。在这项研究中，我们评估了白藜芦醇（Resv）是否通过降低 Tac 免疫抑制作用下的 Th17 反应具有免疫抑制作用。
我们研究了 Resv 在 Tac 治疗条件下对外周血单个核细胞（PBMCs）中 CD4 T 细胞向 Th17 细胞分化以及与人类肾近端管状上皮细胞（HRPTEpiC）共培养的 CD4 T 细胞增殖的影响。在鼠皮肤移植模型中测试了 Resv 对 Th17 细胞的作用。
在 PBMCs 中，Tac 没有，但 Tac 和 Resv 的联合进一步抑制了 Th17 免疫反应。在共培养研究中，与 Tac 单独相比，Resv 与 Tac 的联合显著降低了 HRPTEpiC 诱导的 T 细胞增殖。Resv 处理 Jurkat 细胞诱导 AMP 激活蛋白激酶的表达，并抑制雷帕霉素靶蛋白（mTOR）的表达，表明 Resv 通过阻断 Th17 途径。在鼠皮肤移植模型中，与 Tac 单独或对照组相比，Resv 与 Tac 的联合显著延长了皮肤移植物的存活时间，并伴有 Th17 细胞的抑制。
我们的研究结果表明，Resv 通过抑制移植环境中的效应性 CD4 T 细胞，特别是 Th17 细胞，为 Tac 提供了额外的免疫抑制作用。
