title: Medicinal herbs Fructus corni and Semen cuscutae suppress allograft rejection via distinct immune mechanisms.
abstract: Achieving long-term allograft survival without continuous global immunosuppression is highly desirable because constant immunosuppression causes severe side effects. Traditional Chinese medicine (TCM) has been utilized to treat numerous diseases for centuries. To seek novel immunosuppressive agents, we investigated several Chinese herbal formulas that have been shown to be effective in treating autoimmune diseases. C57BL/6 mice were transplanted with a skin graft from Balb/C donors and treated orally with the TCM. IL-12-expressing dendritic cells and CD4+FoxP3+ Tregs were quantified by flow cytometer while intragraft IL-12 gene expression was measured by real-time PCR. Here we identified a unique TCM, San Si formula, which contains three herbs: Fructus corni (FC), Fructus ligustri lucidi (FLL) and Semen cuscutae (SC). We found that either SC or FC, but not FLL, significantly prolonged skin allograft survival while SC plus FC or San Si formula further delayed allograft rejection compared to SC or FC alone. SC and FC, which did not contain cyclosporine and rapamycin, reduced graft-infiltrating T cells and suppressed their proliferation. Importantly, it was SC, but not FC, that induced CD4+FoxP3+ Tregs in recipients. Tregs induced by SC were also more potent in suppression. In contrast, FC repressed both intracellular IL-12 expression by intragraft DCs and IFNγ expression by graft-infiltrating T cells. Moreover, FC inhibited intragraft IL-12 gene expression. Depleting Tregs and providing exogenous IL-12 completely reversed allograft survival induced by SC plus FC. Thus, SC and FC synergistically suppress allograft rejection via distinct mechanisms.
authors.affiliation: Department of Nephrology, The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.
authors.forename: Xusheng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Nephrology, The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.
authors.forename: Yu-Qun
authors.initials: YQ
authors.lastname: Zeng
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.
authors.forename: Yong-Zhuo
authors.initials: YZ
authors.lastname: Liang
authors.affiliation: Department of Nephrology, The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Zou
authors.affiliation: Section of Immunology, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, P.R. China.
authors.forename: Huazhen
authors.initials: H
authors.lastname: Liu
authors.affiliation: Section of Immunology, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, P.R. China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Qiu
authors.affiliation: Section of Immunology, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, P.R. China.
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Liang
authors.affiliation: Section of Immunology, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, P.R. China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Jin
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.
authors.forename: Zi-Ren
authors.initials: ZR
authors.lastname: Su
authors.affiliation: Department of Nephrology, The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, P.R. China.|Section of Immunology, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, P.R. China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Dai
mesh_terms: D064591:Allografts / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D000818:Animals; D029768:Cornus / Q000737:chemistry*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006084:Graft Rejection / Q000188:drug therapy*; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000378:metabolism; D008516:Medicine, Chinese Traditional / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D016038:Skin Transplantation / Q000009:adverse effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous / Q000009:adverse effects
chemical_list: D004365:Drugs, Chinese Herbal; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007166:Immunosuppressive Agents; D018664:Interleukin-12
keywords: Immune response; Immunity; Immunology and Microbiology Section; T cells; herbs and transplantation; immunosuppression