PMID- 30832648 OWN - NLM STAT- MEDLINE DCOM- 20190321 LR - 20211204 IS - 1472-6882 (Electronic) IS - 1472-6882 (Linking) VI - 19 IP - 1 DP - 2019 Mar 4 TI - Effects of resveratrol on Th17 cell-related immune responses under tacrolimus-based immunosuppression. PG - 54 LID - 10.1186/s12906-019-2464-1 [doi] LID - 54 AB - 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. FAU - Doh, Kyoung Chan AU - Doh KC AD - Convergent Research Consortium for Immunologic disease, St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. AD - Transplant research center, St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. FAU - Kim, Bo-Mi AU - Kim BM AD - Convergent Research Consortium for Immunologic disease, St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. AD - Transplant research center, St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. FAU - Kim, Kyoung Woon AU - Kim KW AD - Convergent Research Consortium for Immunologic disease, St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. AD - Transplant research center, St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. FAU - Chung, Byung Ha AU - Chung BH AD - Convergent Research Consortium for Immunologic disease, St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. AD - Transplant research center, St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. AD - Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. FAU - Yang, Chul Woo AU - Yang CW AUID- ORCID: 0000-0001-9796-636X AD - Convergent Research Consortium for Immunologic disease, St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. yangch@catholic.ac.kr. AD - Transplant research center, St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. yangch@catholic.ac.kr. AD - Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. yangch@catholic.ac.kr. LA - eng GR - HI13C1232/the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea/ GR - HI14C3417/the Korean Health Technology R&D Project, Ministry for Health & Welfare, Republic of Korea/ PT - Journal Article DEP - 20190304 PL - England TA - BMC Complement Altern Med JT - BMC complementary and alternative medicine JID - 101088661 RN - 0 (Immunosuppressive Agents) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - Q369O8926L (Resveratrol) RN - WM0HAQ4WNM (Tacrolimus) SB - IM MH - AMP-Activated Protein Kinases/metabolism MH - Adult MH - Animals MH - Cell Differentiation/drug effects MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Graft Survival/drug effects MH - Humans MH - Immunosuppressive Agents/*pharmacology MH - Leukocytes, Mononuclear/drug effects/metabolism MH - Male MH - Mice MH - Resveratrol/*pharmacology MH - Skin Transplantation MH - TOR Serine-Threonine Kinases/metabolism MH - Tacrolimus/*pharmacology MH - Th17 Cells/*drug effects/immunology/metabolism PMC - PMC6399827 OTO - NOTNLM OT - AMPK OT - Organ transplantation OT - Resveratrol OT - Tacrolimus OT - Th17 cells OT - mTOR COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The Institutional Review Board of Seoul St. Mary's Hospital (KC14TISI0242) approved the experimental protocol of this study. Furthermore, a written consent was sorted from volunteers. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2019/03/06 06:00 MHDA- 2019/03/22 06:00 PMCR- 2019/03/04 CRDT- 2019/03/06 06:00 PHST- 2017/08/31 00:00 [received] PHST- 2019/02/25 00:00 [accepted] PHST- 2019/03/06 06:00 [entrez] PHST- 2019/03/06 06:00 [pubmed] PHST- 2019/03/22 06:00 [medline] PHST- 2019/03/04 00:00 [pmc-release] AID - 10.1186/s12906-019-2464-1 [pii] AID - 2464 [pii] AID - 10.1186/s12906-019-2464-1 [doi] PST - epublish SO - BMC Complement Altern Med. 2019 Mar 4;19(1):54. doi: 10.1186/s12906-019-2464-1.