Renal tubular epithelial cells as immunoregulatory cells in renal allograft rejection

Kidney transplantation is the best therapeutic option for patients with end-stage kidney disease. However, the long-term survival of kidney transplants still remains relatively poor even under potent immunosuppression. Thus, it is necessary to further review the pathogenesis of renal allograft failure. Here, we discuss the potential impact of activated resident tubular epithelial cells (TECs) on infiltrating leukocyte responses on renal allograft failure. Immunohistochemical staining or in situ hybridization of renal allograft biopsies shows that activated TECs produce inflammatory cytokines and may act as nonprofessional antigen-presenting cells in the response to stimulation from leukocyte infiltration. Further experimental studies confirm that by a feedback loop, activated TECs positively or negatively regulate the destructive activity of infiltrating leukocyte through (1) alteration of leukocyte activation, proliferation, differentiation, and migration to the graft through secretion of cytokines and chemokines; and (2) direct regulation of infiltrating T-cell function through cell-cell contact. Specifically targeting kidney factors has significant impact on renal graft damage or kidney disease. This review suggests that graft TECs can regulate intragraft immune responses, and modulation of specific graft TEC responses as a therapeutic strategy may benefit long-term survival of kidney transplants.