Medicinal herbs Fructus corni and Semen cuscutae suppress allograft rejection via distinct immune mechanisms

Autor: Chuan Zou, Xusheng Liu, Feifei Qiu, Zhenhua Dai, Huazhen Liu, Yu-Qun Zeng, Zi-Ren Su, Yong-Zhuo Liang, Xiao-Wei Jin, Chun-Lin Liang
Rok vydání: 2016
Předmět:
Graft Rejection
0301 basic medicine
medicine.medical_treatment
T cells
Semen
Traditional Chinese medicine
030230 surgery
Real-Time Polymerase Chain Reaction
T-Lymphocytes
Regulatory
Mice
03 medical and health sciences
Cornus
0302 clinical medicine
Immune system
herbs and transplantation
Immunity
Gene expression
Animals
Humans
Transplantation
Homologous
Medicine
Immune response
Medicine
Chinese Traditional
Immunosuppression Therapy
Mice
Inbred BALB C
immunosuppression
business.industry
Graft Survival
Research Paper: Immunology
FOXP3
Drug Synergism
Forkhead Transcription Factors
Immunosuppression
Dendritic Cells
Skin Transplantation
Allografts
Interleukin-12
Mice
Inbred C57BL
030104 developmental biology
Oncology
Immunology
Immunology and Microbiology Section
Drug Therapy
Combination
business
Immunosuppressive Agents
Intracellular
Drugs
Chinese Herbal
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: 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.
Databáze: OpenAIRE
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