Abstract
Allograft rejection after renal transplantation remains a challenge to overcome. Interleukin (IL)-21, a cytokine with pleiotropic effects, maintains immune homeostasis post-transplantation. Here, we report higher levels of IL-21 in kidney transplant recipients with non-rejection (NR) than in recipients with T cell-mediated rejection (TCMR, P < 0.001) and antibody-mediated rejection (ABMR, P = 0.005). We observed a negative correlation between IL-21 and creatinine (Cr) levels (P = 0.016). The receiving operating characteristic (ROC) curve showed a promising diagnostic value of IL-21 to identify acute rejection with an area under the curve (AUC) of 0.822 (P < 0.001). In contrast, exogenous administration of IL-21 accelerated acute rejection in a comparative translational kidney transplant (KT) mouse model. Reduced IL-21 levels in the peripheral blood were observed in KT mice after IL-21 injection. Further analysis revealed that increased IL-21 levels in the spleen induced proliferation of CD4+ T cells and CD19+ B cells after IL-21 treatment. Our findings suggest a critical function of IL-21 in kidney transplantation and the potential involvement of the IL-21/IL-21R pathway in acute rejection management.
Highlights
Allograft rejection remains one of the major barriers to the long-term survival of the graft
There was no difference among non-rejection (NR), T cell-mediated rejection (TCMR), and antibody-mediated rejection (ABMR) cohorts regarding the donor-associated parameters, recipient’s age, primary kidney disease, dialysis, delayed graft function (DGF) rate, or HLA-mismatch (HLA-MM)
The levels of IL-21, which is widely considered as a driving factor of germinal centers (GCs) B cell differentiation, were lower in acute rejection patients (11.02±0.29 pg/mL) than in immune stable patients (18.21±2.00 pg/mL, P < 0.001) (Figure 1G)
Summary
Allograft rejection remains one of the major barriers to the long-term survival of the graft. More potent immunosuppressive drugs and better histocompatibility between recipients and donors have altered the characteristics of allograft rejection. The risk of rejection within 1 year after kidney transplantation has declined to less than www.aging-us.com. The overall graft survival rates have still not improved due to the intractability of rejection [2]. Rejection could be divided into T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) [1]. Patients with emerging rejection face an increased risk of graft failure, especially ABMR [3, 4]
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