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Elevated Serum Il-21 Levels Are Associated With Stable Immune Status In Kidney Transplant Recipients And A Mouse Model Of Kidney Transplantation, Luying Guo, Junhao Lv, Jian Zhang, Hao Deng, Shi Feng, Shuaihui Liu, Pengpeng Yan, Jingyi Zhou, Hui Chen, Meifang Wang, Qin Zhou, Huiping Wang, Jianghua Chen, Yu Kuang, Jia Shen, Rendwing Wang

School of Medicine Faculty Publications

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.