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.
Highlights
An allograft is always rejected in the absence of continuously immunosuppressive treatments, which generally cause various side effects
Skin allografts derived from Balb/C mice were transplanted to C57BL/6 mice that were treated with www.impactjournals.com/oncotarget
Fructus ligustri lucidi (FLL) alone did not delay skin allograft rejection compared to the control (MST = 11 vs. 12 days)
Summary
An allograft is always rejected in the absence of continuously immunosuppressive treatments, which generally cause various side effects. Achieving long-term allograft survival without long-term treatments with any global immunosuppressive agent is highly desired in organ transplantation. Extensive studies are needed to seek more effective TCM to inhibit allograft rejection. We investigated several Chinese herbal formulas that have never been published despite their clinical utilization. They have been shown to be highly effective in treating some autoimmune diseases according to testimonies of numerous patients as well as some of the well-recognized physicians specialized in TCM. We found that two herbal components from San Si formula, Fructus corni (FC) and Semen cuscutae (SC), significantly delayed murine skin allograft rejection. It was FC that inhibited Th1 responses by repressing IL-12 expression in dendritic cells (DCs), whereas SC induced CD4+FoxP3+ regulatory T cells (Treg) that were more potent in suppression
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
