Mechanisms of natural killer cell-mediated clearance of senescent renal tubular epithelial cells

Introduction: Intact kidney function is essential for fluid and electrolyte
homeostasis, with renal tubular epithelial cells providing critical functions in the
reabsorption or secretion of numerous metabolites. Cellular senescence of the
renal epithelial cells can lead to functional deficits. Therefore, immune-cellmediated
clearance of senescent epithelial cells can be an important factor for
the maintenance of kidney function.
Methods: In this study, we established a model to directly monitor natural killer
(NK) cell-mediated clearance of senescent renal tubular cells. To this end we
used primary cell co-cultures with different read-outs and life cell imaging.
Results and Discussion: We observed that the clustering of NK cells on
senescent renal epithelial cells could be used to detect senescence-triggered
NK cell activation. Also, we found that NKG2D signaling and perforin-dependent
lysis of senescent renal epithelial cells were crucial steps in the lysis of senescent
cells. In addition, NK cell-mediated attack of senescent renal epithelial cells
could be dampened by the addition of cyclosporine A and was augmented by the
addition of interleukin 7. Together, these data show that NK cells can efficiently
mediate the clearance of senescent renal tubular epithelial cells involving NK
cell activation by NKG2D signaling.