Research Paper Volume 12, Issue 18 pp 18396—18414
Elevated serum IL-21 levels are associated with stable immune status in kidney transplant recipients and a mouse model of kidney transplantation
- 1 Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China
- 2 National Key Clinical Department of Kidney Diseases, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China
- 3 Zhejiang Provincial Key Laboratory of Kidney Disease Prevention and Control Technology, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China
- 4 Zhejiang University Institute of Nephrology, Hangzhou 310003, Zhejiang, China
- 5 The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China
- 6 Medical Physics Program, University of Nevada, Las Vegas, NV 89154, USA
- 7 Organ Donation and Coordination Office, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China
Received: April 8, 2020 Accepted: June 29, 2020 Published: September 29, 2020https://doi.org/10.18632/aging.103713
How to Cite
Copyright: © 2020 Guo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.