PMID- 32472435 OWN - NLM STAT- MEDLINE DCOM- 20210713 LR - 20210713 IS - 1568-5608 (Electronic) IS - 0925-4692 (Print) IS - 0925-4692 (Linking) VI - 28 IP - 6 DP - 2020 Dec TI - Paeoniflorin ameliorates ulcerative colitis by modulating the dendritic cell-mediated T(H)17/T(reg) balance. PG - 1705-1716 LID - 10.1007/s10787-020-00722-6 [doi] AB - Immunological tolerance is critical for maintaining gut homeostasis. An imbalance between interleukin-17 (IL-17)-producing T helper 17 (T(H)17) cells and regulatory T cells (T(reg) cells) is involved in ulcerative colitis (UC) pathogenesis. Dendritic cells (DCs) are able to induce T cell differentiation. Paeoniflorin (PF) is a monoterpene glucoside that is commonly used for treatment of autoimmune disease. However, the immunological mechanism of PF involvement in UC treatment is unclear. The present study aimed to explore whether PF can restore the T(H)17/T(reg) balance by modulating DCs. The effects of PF on DCs, T(H)17 cells and T(reg) cells were measured. Furthermore, PF-treated DCs were injected into mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. PF inhibited MHC-II and CD86 expression on the DC surface (P < 0.05), decreased interleukin (IL)-12 secretion in vitro and in vivo (P < 0.05), and restored the T(H)17/T(reg) ratio in the mouse model of colitis (P < 0.05). PF-treated DCs diminished T(H)17 differentiation (4.26% in vitro and 1.64% in vivo) and decreased IL-17 expression (P < 0.05) while inducing CD4(+)CD25(+)Foxp3(+) T(reg) differentiation (7.82% in vitro and 6.85% in vivo) and increasing Foxp3 and IL-10 production (P < 0.05). Additionally, both PF and PF-treated DCs improved colonic histopathology in the mouse model of colitis (P < 0.05). In conclusion this study suggested that PF can ameliorate TNBS-induced colitis by modulating the DC-mediated T(H)17/T(reg) balance. FAU - Zheng, Kai AU - Zheng K AUID- ORCID: 0000-0001-7005-0271 AD - Department of Gastroenterology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. pajo@163.com. FAU - Jia, Jia AU - Jia J AD - Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. FAU - Yan, Shihai AU - Yan S AD - Laboratory of Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. FAU - Shen, Hong AU - Shen H AD - Department of Gastroenterology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. FAU - Zhu, Ping AU - Zhu P AD - Department of Colon and Rectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. FAU - Yu, Jiangyi AU - Yu J AD - Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. tcmstudy@163.com. LA - eng GR - 81873250/National Natural Science Foundation of China/ GR - 81704022/National Natural Science Foundation of China/ GR - 81403343/National Natural Science Foundation of China/ PT - Journal Article DEP - 20200529 PL - Switzerland TA - Inflammopharmacology JT - Inflammopharmacology JID - 9112626 RN - 0 (Forkhead Transcription Factors) RN - 0 (Glucosides) RN - 0 (Interleukin-17) RN - 0 (Monoterpenes) RN - 130068-27-8 (Interleukin-10) RN - 21AIQ4EV64 (peoniflorin) RN - 8T3HQG2ZC4 (Trinitrobenzenesulfonic Acid) SB - IM MH - Animals MH - Autoimmune Diseases/drug therapy/metabolism MH - Cell Differentiation/drug effects MH - Colitis, Ulcerative/*drug therapy/metabolism MH - Dendritic Cells/*drug effects/metabolism MH - Disease Models, Animal MH - Forkhead Transcription Factors/metabolism MH - Glucosides/metabolism/*pharmacology MH - Interleukin-10/metabolism MH - Interleukin-17/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Monoterpenes/*pharmacology MH - T-Lymphocytes, Regulatory/*drug effects/metabolism MH - Th17 Cells/*drug effects/metabolism MH - Trinitrobenzenesulfonic Acid/pharmacology PMC - PMC7572351 OTO - NOTNLM OT - Dendritic cells OT - Immunological tolerance OT - Paeoniflorin OT - TH17 OT - Treg OT - Ulcerative colitis COIS- The authors declare that they have no conflicts of interest. EDAT- 2020/05/31 06:00 MHDA- 2021/07/14 06:00 PMCR- 2020/05/29 CRDT- 2020/05/31 06:00 PHST- 2019/11/17 00:00 [received] PHST- 2020/05/11 00:00 [accepted] PHST- 2020/05/31 06:00 [pubmed] PHST- 2021/07/14 06:00 [medline] PHST- 2020/05/31 06:00 [entrez] PHST- 2020/05/29 00:00 [pmc-release] AID - 10.1007/s10787-020-00722-6 [pii] AID - 722 [pii] AID - 10.1007/s10787-020-00722-6 [doi] PST - ppublish SO - Inflammopharmacology. 2020 Dec;28(6):1705-1716. doi: 10.1007/s10787-020-00722-6. Epub 2020 May 29.