Role of Immune Cells in Acute Kidney Injury and Repair

Abstract

Acute kidney injury (AKI) is a significant problem in both native and transplant kidneys. There have been significant advances in understanding the role of immune cells in the early injury and repair from AKI. In this brief review, we aim to update information on the pathophysiologic impact of various immune cells in AKI, with special emphasis on repair. An improved understanding of the AKI immunopathology will lead to new therapies that prevent AKI, accelerate repair, and prevent the progression of AKI to chronic kidney disease.

Keywords: Acute kidney injury; B lymphocyte; Dendritic cells; Double-negative T cells; Immune cells; Inflammation; Kidney repair; Macrophage; Neutrophil; Regulatory T cells; T lymphocyte.

Figure 1

Several types of resident immune cells are present in the normal kidney. After renal injury, very early inflammation is likely initiated by the resident immune cells, which is followed by rapid infiltration of circulating immune cells in response to the inflammatory cytokines and chemokines secreted from activated/damaged resident cells. DAMPs and PAMPs secreted from damaged cells enhance immune cell recruitment to injured kidney tissue and participate in the establishment of initial tissue injury in early AKI. Abbreviations: AKI, acute kidney injury; DN T cell, double negative T cell; DAMPs, damage-associated molecular patterns; PAMPs, pathogen-associated molecular patterns; PRP, pattern recognition receptor. Modified from Jang, H.R. & Rabb, H. Immune cells in experimental acute kidney injury, Nature reviews Nephrology. 2015;11:88-101

Figure 2

The regional immunologic response after AKI determines the consequence of renal injury, either in tissue repair and regeneration or in chronic inflammation with renal fibrosis. During adaptive repair, reparatory responses occur to restore the normal structure and tissue homeostasis in the kidney. Tolerogenic DCs, M2 macrophages and regulatory T cells modulate the renal immune response by direct cell-cell contact or by humoral mediators, leading to endothelial and renal tubular repair and regeneration. However, when there is prolonged or severe AKI, maladaptive repair process begins resulting in chronic inflammation and tissue fibrosis. Inflammatory cells continue to infiltrate into renal interstitium with secretion of pro-inflammatory/pro-fibrotic cytokines. Growth-arrested tubular cells also participate in the formation of pro-fibrotic renal microenvironment with secretion of profibrotic cytokines and growth factors. The interaction of pericyte and endothelial cells is impaired due to endothelial injury during AKI, which leads to activation and proliferation of pericytes. Active pericytes evolve into scar-producing myofibroblasts, which induces renal fibrosis and clinically leads to chronic kidney disease. Abbreviations: AKI, acute kidney injury; DCs, dendritic cells; DN T cell, double negative T cell. Modified from Jang, H.R. & Rabb, H. Immune cells in experimental acute kidney injury, Nature reviews Nephrology. 2015;11:88-101