Abstract
Background: Dendritic cells (DCs) serve as an important part of the immune system and play a dual role in immune response. Mature DCs can initiate immune response, while immature or semi-mature DCs induce immune hyporesponsiveness or tolerance. Previous studies have shown that aspirin can effectively inhibit the maturation of DCs. However, the protective effect of aspirin on acute cardiac allograft rejection has not been studied. The aim of this study was to elucidate the effect of aspirin exert on allograft rejection.Methods: The model of MHC-mismatched (BALB/c to B6 mice) heterotopic heart transplantation was established and administered intraperitoneal injection with aspirin. The severity of allograft rejection, transcriptional levels of cytokines, and characteristics of immune cells were assessed. Bone marrow-derived dendritic cells (BMDCs) were generated with or without aspirin. The function of DCs was determined via mixed lymphocyte reaction (MLR). The signaling pathway of DCs was detected by Western blotting.Results: Aspirin significantly prolonged the survival of cardiac allograft in mouse, inhibited the production of pro-inflammatory cytokines and the differentiation of effector T cells (Th1 and Th17), as well as promoted the regulatory T cells (Treg). The maturation of DCs in the spleen was obviously suppressed with aspirin treatment. In vitro, aspirin decreased the activation of NF-κB signaling of DCs, as well as impeded MHCII and co-stimulatory molecules (CD80, CD86, and CD40) expression on DCs. Moreover, both the pro-inflammatory cytokines and function of DCs were suppressed by aspirin.Conclusion: Aspirin inhibits the maturation of DCs through the NF-κB signaling pathway and attenuates acute cardiac allograft rejection.
Highlights
With the tremendous advance in the field of organ transplantation over the past half century, heart transplantation has become the standard therapy for end-stage heart failure (Stehlik et al, 2018), and the much-improved immunosuppressive agents effectively prolong the survival of patients after transplantation (Chen et al, 2020)
Aspirin decreased the activation of NF-κB signaling of Dendritic cells (DCs), as well as impeded major histocompatibility complex II (MHCII) and co-stimulatory molecules (CD80, CD86, and CD40) expression on DCs
Aspirin inhibits the maturation of DCs through the NF-κB signaling pathway and attenuates acute cardiac allograft rejection
Summary
With the tremendous advance in the field of organ transplantation over the past half century, heart transplantation has become the standard therapy for end-stage heart failure (Stehlik et al, 2018), and the much-improved immunosuppressive agents effectively prolong the survival of patients after transplantation (Chen et al, 2020). The mortality associated with acute allograft rejection and subclinical episodes concerning allograft dysfunction still seriously affected the long-term survival of patients (Benza et al, 2009). Controlling the maturation of DCs has a great potential in regulating cardiac allograft rejection. Previous studies have well established that manipulated immature or semi-mature DCs effectively prolong the allograft survival after heart transplantation (Takenaka and Quintana, 2017; Iberg and Hawiger, 2020). Mature DCs can initiate immune response, while immature or semi-mature DCs induce immune hyporesponsiveness or tolerance. Previous studies have shown that aspirin can effectively inhibit the maturation of DCs. the protective effect of aspirin on acute cardiac allograft rejection has not been studied. The aim of this study was to elucidate the effect of aspirin exert on allograft rejection
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