Yan Liu1, Yan Chen, Jonathan R Lamb, Paul K H Tam. 1. Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, PR China.
Abstract
BACKGROUND: Triptolide (TPT) is a component of the Chinese herb Triptergium wilfordii and has potent immunosuppressive and anti-inflammatory effects. Since dendritic cells (DCs) play a critical role in the initiation of alloimmune responses to foreign grafts, the aim of the present study was to evaluate the effects of TPT in the functional phenotype of bone marrow (BM)-derived DCs. METHODS: BM-derived DCs were cultured with or without TPT from days 2 to 7 and then stimulated with lipopolysaccharide (LPS) for a further 2 days. In some experiments, TPT was added to the cultures from day 7 to day 9. Heterotopic cardiac transplantation was performed and animals received either no treatment or were injected systemically with different doses of TPT posttransplantation. RESULTS: TPT treatment inhibited LPS-induced DC maturation. The ability of DCs to stimulate allogeneic T-cell responses was also impaired by TPT treatment and accompanied by upregulated synthesis of interleukin-10 facilitating the expansion of regulatory T cells. Furthermore, we observed that TPT treatment led to increased cell surface expression of DC-SIGN and reduced expression of TLR4 on DCs. CONCLUSIONS: These findings demonstrate that TPT can inhibit the maturation and allogenicity of DCs and promotes the expansion of regulatory T cells. These effects were confirmed by in vivo experiments though treatment of TPT can prolong mice heart allograft survival. Furthermore, modulation of the DC surface phenotype towards that of a tolerogenic phenotype could contribute to the ability of TPT to suppress productive immunity and maintain homeostasis.
BACKGROUND:Triptolide (TPT) is a component of the Chinese herb Triptergium wilfordii and has potent immunosuppressive and anti-inflammatory effects. Since dendritic cells (DCs) play a critical role in the initiation of alloimmune responses to foreign grafts, the aim of the present study was to evaluate the effects of TPT in the functional phenotype of bone marrow (BM)-derived DCs. METHODS: BM-derived DCs were cultured with or without TPT from days 2 to 7 and then stimulated with lipopolysaccharide (LPS) for a further 2 days. In some experiments, TPT was added to the cultures from day 7 to day 9. Heterotopic cardiac transplantation was performed and animals received either no treatment or were injected systemically with different doses of TPT posttransplantation. RESULTS:TPT treatment inhibited LPS-induced DC maturation. The ability of DCs to stimulate allogeneic T-cell responses was also impaired by TPT treatment and accompanied by upregulated synthesis of interleukin-10 facilitating the expansion of regulatory T cells. Furthermore, we observed that TPT treatment led to increased cell surface expression of DC-SIGN and reduced expression of TLR4 on DCs. CONCLUSIONS: These findings demonstrate that TPT can inhibit the maturation and allogenicity of DCs and promotes the expansion of regulatory T cells. These effects were confirmed by in vivo experiments though treatment of TPT can prolong mice heart allograft survival. Furthermore, modulation of the DC surface phenotype towards that of a tolerogenic phenotype could contribute to the ability of TPT to suppress productive immunity and maintain homeostasis.
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