Abstract
Natural killer (NK) cells are a specialized population of innate lymphocytes that have a major effector function in local immune responses. While their immunological functions in many inflammatory diseases are well established, comparatively little is still known about their roles in kidney homeostasis and disease. Our understanding of kidney NK cells is rapidly evolving, with murine studies highlighting the functional significance of NK cells in acute and chronic forms of renal disease. Recent progress has been made in translating these murine findings to human kidneys, with indications of NK cell subset-specific roles in disease progression in both native and allograft kidneys. Clearly, a better understanding of the molecular mechanisms driving NK cell activation and importantly, their downstream interactions with intrinsic renal cells and infiltrating immune cells is necessary for the development of targeted therapeutics to halt disease progression. In this review, we discuss the properties and potential functions of kidney NK cells.
Highlights
Kidney disease is a major public health problem, affecting ∼10% of populations in industrialized countries [1]
While Natural killer (NK) cells are likely to play a role in interstitial renal fibrosis in chronic kidney disease (CKD), the evidence to support a substantial role of NK cells in glomerulonephritis is still scarce and detailed functional analyses of kidney NK cell subsets in glomerulonephritis with state-of-the-art methods are still missing
Emerging transcriptomic evidence indicates that NK cell activation in antibody-mediated rejection (ABMR) biopsies is mediated via IgG Fc receptor CD16 triggering [58]. These findings have led to a proposed pathogenic function for NK cells in human ABMR, whereby donor-specific antibodies (DSA) bound to allograft endothelial cells will engage with CD16 on NK cells to induce a mechanism of antibody-dependent cell-mediated cytotoxicity directed against the allograft (Figure 3)
Summary
Jan-Eric Turner 1*†, Constantin Rickassel 1, Helen Healy 2,3 and Andrew J. Natural killer (NK) cells are a specialized population of innate lymphocytes that have a major effector function in local immune responses. While their immunological functions in many inflammatory diseases are well established, comparatively little is still known about their roles in kidney homeostasis and disease. Our understanding of kidney NK cells is rapidly evolving, with murine studies highlighting the functional significance of NK cells in acute and chronic forms of renal disease. A better understanding of the molecular mechanisms driving NK cell activation and importantly, their downstream interactions with intrinsic renal cells and infiltrating immune cells is necessary for the development of targeted therapeutics to halt disease progression.
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