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.
Highlights
Infections are known to induce various types of kidney injury
We aim to introduce our current understanding of the association among infections, Natural killer T (NKT) as with murine NKT (and NK) cells, and kidney injury, which is much more profound than previously thought
In our recent study using peripheral blood mononuclear cells (MNCs) stimulated by IL-2, IL-12, and IL-15, we showed that CD56bright cells substantially injure renal tubular epithelial cells in vitro; the cytotoxicity of CD56bright NK cells was significantly higher than that of CD56dim cells and conventional T cells [8]
Summary
Infections are known to induce various types of kidney injury. One of the most common types is acute kidney injury (AKI) [1], which in turn causes the dysfunction of distant organs, such as the lung or heart [2]. This unique function of NKT cells is in sharp contrast to the function of conventional T cells, which detect antigens (mainly peptides) presented on MHC molecules, and are comprised of two functionally distinct subsets, namely, Th1 and Th2 cells When these cells are stimulated by cytokines or bacterial components, such as lipopolysaccharide (LPS), superantigens of gram-positive bacteria, or streptococcal derivatives, they play important roles in the defense against tumors and infections; i.e., both NKT and NK cells exert cytotoxic activity simultaneously or differentially by releasing cytotoxic mediators, such as perforin and granzyme, and/or by producing proinflammatory cytokines, including interferon-gamma (IFN-γ), depending on the type of stimuli [10]. The roles of two types of liver macrophages in the activation/regulation of NKT cells are discussed
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