Infections, Reactions of Natural Killer T Cells and Natural Killer Cells, and Kidney Injury

Abstract

Natural killer T (NKT) cells and NK cells are representative innate immune cells that perform antitumor and antimicrobial functions. The involvement of these cells in various renal diseases, including acute kidney injury (AKI), has recently become evident. Murine NKT cells are activated and cause AKI in response to various stimuli, such as their specific ligand, cytokines, and bacterial components. Both renal vascular endothelial cell injury (via the perforin-mediated pathway) and tubular epithelial cell injury (via the tumor necrosis factor-alpha/Fas ligand pathway) are independently involved in the pathogenesis of AKI. NK cells complement the functions of NKT cells, thereby contributing to the development of infection-associated AKI. Human CD56+ T cells, which are a functional counterpart of murine NKT cells, as well as a subpopulation of CD56+ NK cells, strongly damage intrinsic renal cells in vitro upon their activation, possibly through mechanisms similar to those in mice. These cells are also thought to be involved in the acute exacerbation of pre-existing glomerulonephritis triggered by infection in humans, and their roles in sepsis-associated AKI are currently under investigation. In this review, we will provide an overview of the recent advances in the understanding of the association among infections, NKT and NK cells, and kidney injury, which is much more profound than previously considered. The important role of liver macrophages in the activation of NKT cells will also be introduced.

Involvement of M1-Activated Macrophages and Perforin/Granulysin Expressing Lymphocytes in IgA Vasculitis Nephritis

“…NK cells in the tubules may be responsible for perforin-mediated necrosis of tubular epithelial cells, as damaged tubular epithelial cells were labelled with an antiperforin antibody in our experiments, and perforin-mediated acute tubular necrosis is a mechanism of tubular damage in IgAVN [26]. A similar observation was made in the kidney during acute postinfectious glomerulonephritis, focal necrotising (pauci-immune) glomerulonephritis [30], acute kidney rejection [31], or infection [32], indicating strong cell-mediated immunity in IgAVN. Additionally, we observed granulysin expression in glomerular and intratubular CD56+ cells but not in interstitial CD56+ cells, suggesting an apoptotic mechanism of tubular damage, primarily by CD56+ cells of glomerular origin, as observed in the acute rejection of kidney transplants resistant to glucocorticoid treatment [21].…”

Involvement of Innate Immune System in the Pathogenesis of Sepsis-Associated Acute Kidney Injury

“…Both CD56 + T and NK cells pro hold large amounts of cytotoxic effector molecules, including FasL and perfori A study previously reported that both serum and urine FasL levels were increased in the early disease stage in an SA-AKI model [12]. In addition, we have previously shown that mouse NKT cells activated by their specific ligand or bacterial components caused AKI by damaging the renal tubular epithelial cells via the TNF-α/FasL pathway [13]. Consistent with these results, in the present study, FasL expression on CD56 + T cells, a functional counterpart of mouse NKT cells, was significantly upregulated in patients with SA-AKI compared to healthy controls.…”

Preoperative inflammatory biomarkers reveal renal involvement in postsurgical mortality in hip fracture patients: an exploratory study

“…There is now a substantial body of evidence showing that NK cells contribute to kidney injury and kidney failure by contributing to acute tubular necrosis in humans ( 57 , 59 , 60 ). Thus, it is likely that the effect of IL-15RA might be mediated by the role of its ligand on NK cells.…”