title: Generation of regulatory dendritic cells after treatment with paeoniflorin.
abstract: Regulatory dendritic cells are a potential therapeutic tool for assessing a variety of immune overreaction diseases. Paeoniflorin, a bioactive glucoside extracted from the Chinese herb white paeony root, has been shown to be effective at inhibiting the maturation and immunostimulatory function of murine bone marrow-derived dendritic cells. However, whether paeoniflorin can program conventional dendritic cells toward regulatory dendritic cells and the underlying mechanism remain unknown. Here, our study demonstrates that paeoniflorin can induce the production of regulatory dendritic cells from human peripheral blood monocyte-derived immature dendritic cells in the absence or presence of lipopolysaccharide (LPS) but not from mature dendritic cells, thereby demonstrating the potential of paeoniflorin as a specific immunosuppressive drug with fewer complications and side effects. These regulatory dendritic cells treated with paeoniflorin exhibited high CD11b/c and low CD80, CD86 and CD40 expression levels as well as enhanced abilities to capture antigen and promote the proliferation of CD4(+)CD25(+) T cells and reduced abilities to migrate and promote the proliferation of CD4(+) T cells, which is associated with the upregulation of endogenous transforming growth factor (TGF)-β-mediated indoleamine 2,3-dioxygenase (IDO) expression. Collectively, paeoniflorin could program immature dendritic cells (imDCs) and imDCs stimulated with LPS toward a regulatory DC fate by upregulating the endogenous TGF-β-mediated IDO expression level, thereby demonstrating its potential as a specific immunosuppressive drug.
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Basic Medical College, Tianjin Medical University, Tianjin, 300070, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Biology, School of Basic Medical Sciences, Basic Medical College, Tianjin Medical University, Tianjin, 300070, People's Republic of China.
authors.forename: Yingxi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Basic Medical College, Tianjin Medical University, Tianjin, 300070, People's Republic of China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biology, School of Basic Medical Sciences, Basic Medical College, Tianjin Medical University, Tianjin, 300070, People's Republic of China.
authors.forename: Keqiu
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Biology, School of Basic Medical Sciences, Basic Medical College, Tianjin Medical University, Tianjin, 300070, People's Republic of China.
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Basic Medical College, Tianjin Medical University, Tianjin, 300070, People's Republic of China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Basic Medical College, Tianjin Medical University, Tianjin, 300070, People's Republic of China.
authors.forename: Zhaoyan
authors.initials: Z
authors.lastname: Qiang
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Basic Medical College, Tianjin Medical University, Tianjin, 300070, People's Republic of China.
authors.forename: Jingzhi
authors.initials: J
authors.lastname: Tong
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Basic Medical College, Tianjin Medical University, Tianjin, 300070, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Basic Medical College, Tianjin Medical University, Tianjin, 300070, People's Republic of China.
authors.forename: Wen
authors.initials: W
authors.lastname: Ding
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Basic Medical College, Tianjin Medical University, Tianjin, 300070, People's Republic of China. kangy@tmu.edu.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Department of Biology, School of Basic Medical Sciences, Basic Medical College, Tianjin Medical University, Tianjin, 300070, People's Republic of China. lig@tmu.edu.cn.
authors.forename: Guang
authors.initials: G
authors.lastname: Li
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007165:Immunosuppression Therapy; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology*; D029596:Paeonia / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D006027:Glycosides
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015703:Antigens, CD; D016207:Cytokines; D005960:Glucosides; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008070:Lipopolysaccharides; D039821:Monoterpenes; D016212:Transforming Growth Factor beta; C015423:peoniflorin; D006027:Glycosides
keywords: IDO; Immunomodulation; Paeoniflorin; Regulatory dendritic cells; TGF-β