ScholarWorks@성균관대학교

초록

Acute kidney injury (AKI) is a common and serious disease entity that affects native kidneys and allografts but for which no specific treatments exist. Complex intrarenal inflammatory processes driven by lymphocytes and innate immune cells have key roles in the development and progression of AKI. Many studies have focused on prevention of early injury in AKI. However, most patients with AKI present after injury is already established. Increasing research is therefore focusing on mechanisms of renal repair following AKI and prevention of progression from AKI to chronic kidney disease. CD4+ and CD8+ T cells, B cells and neutrophils are probably involved in the development and progression of AKI, whereas regulatory T cells, double-negative T cells and type 2 innate lymphoid cells have protective roles. Several immune cells, such as macrophages and natural killer T cells, can have both deleterious and protective effects, depending on their subtype and/or the stage of AKI. The immune system not only participates in injury and repair processes during AKI but also has a role in mediating AKI-induced distant organ dysfunction. Targeted manipulation of immune cells is a promising therapeutic strategy to improve AKI outcomes. Here, the authors describe the roles of lymphocytes and innate immune cells in inflammatory responses and repair processes during acute kidney injury (AKI). They also discuss the roles of immune cells in crosstalk pathways that result in AKI-induced distant organ dysfunction. Robust intrarenal inflammatory processes driven by lymphocytes and innate immune cells are important in the pathogenesis of acute kidney injury (AKI); these processes have primarily been studied in ischaemia-reperfusion injury and cisplatin-induced AKI models.CD4+ T cells, B cells, neutrophils, M1 macrophages and type I natural killer T cells mainly exert pro-inflammatory roles in AKI, contributing to injury, whereas regulatory T cells, double-negative T cells, regulatory B cells and type 2 innate lymphoid cells have anti-inflammatory roles.Understanding the role of lymphocytes in kidney repair after AKI is important to enable the development of novel therapeutic agents to accelerate recovery and prevent the development of kidney fibrosis and progression to chronic kidney disease.During kidney repair, effector-memory T cells are probably involved in persistent inflammation and fibrosis, whereas regulatory T cells promote tubular regeneration; B cells and plasma cells also contribute to tubular atrophy and fibrosis, whereas M2 macrophages are a heterogeneous population with both regenerative and profibrotic effects.Increasing evidence suggests that immune cells and their mediators contribute to distant organ dysfunction in AKI, which substantially influences patient outcomes.Novel technologies such as single-cell RNA sequencing, spatial transcriptomics, kidney-on-a-chip and kidney organoids have the potential to revolutionize research on the roles of immune cells in the kidney.

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