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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

Luying Guo1,2,3,4, Junhao Lv1,2,3,4, Jian Zhang1,2,3,4, Hao Deng1,2,3,4, Shi Feng1,2,3,4, Shuaihui Liu1,2,3,4, Pengpeng Yan1,2,3,4, Jingyi Zhou1,2,3,4, Hui Chen5, Meifang Wang1,2,3,4, Qin Zhou1,2,3,4, Huiping Wang1,2,3,4, Jianghua Chen1,2,3,4, Yu Kuang6, Jia Shen1,2,3,4, Rending Wang1,2,3,4,7
  • 1Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China
  • 2National Key Clinical Department of Kidney Diseases, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China
  • 3Zhejiang Provincial Key Laboratory of Kidney Disease Prevention and Control Technology, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China
  • 4Zhejiang University Institute of Nephrology, Hangzhou 310003, Zhejiang, China
  • 5The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China
  • 6Medical Physics Program, University of Nevada, Las Vegas, NV 89154, USA
  • 7Organ Donation and Coordination Office, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China
* Equal contribution
# Co-senior authors
Received: April 8, 2020Accepted: June 29, 2020Published: September 29, 2020

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.

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.