Role of IL-21 signaling pathway in transplant-related biology

Since pro-inflammatory cytokine IL-21 and its receptor (IL-21R) are closely involved in regulating both innate and adaptive immune responses, it is conceivable that they may play important roles in the field of organ transplantation. IL-21/IL21-R regulates immune activities of CD8+ T cells, Tfh cells, Th17 cells, B cells, NK cells, dendritic cells and stimulates dendritic cells to produce high level of IL-6, TNF-alpha, and CCL2. However, their roles and underlying mechanisms remain obscure. Our present study is the first describing the role of IL-21 signaling pathway in transplant biology. It was found that IL-21/IL-21R signaling pathways contribute to the processes of ischemia/reperfusion and acute rejection of liver or kidney transplantation. IL-21 is capable of regulating B cell function and immunoglobulin production, driving CD8+ T cell expansion, regulating Th17 and dendritic cell function. Deficiency of IL-21 may cause autoimmunity and infectious disease in clinical-scenario patients. It is known that CD8+ T cells, Th17, and dendritic cells are closely involved in cardiac transplant tolerance. Our own original experimental research on mouse cardiac transplantation manifested that allograft survival could be significantly prolonged in the IL-21R deficient recipients. All these can deepen our understanding of immunobiological role of IL-21 and its receptor in the field of transplantation. Intervention of IL-21 signaling pathway may apparently regulate immunoresponses in vivo, which can be subsequently utilized as a therapeutic strategy in clinic.