ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cell Growth and Division
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1597230
This article is part of the Research TopicCellular Senescence in Aging-Related Diseases: Mechanisms and Therapeutic TargetsView all 6 articles
Mechanisms of Natural Killer Cell-Mediated Clearance of Senescent Renal Tubular Epithelial Cells
Provisionally accepted
Nils D Funk
Julius Sinning
Inga Soerensen-ZenderVera Christine WulfmeyerKai Schmidt-Ott
Korbinian Brand
Stephan Halle*
Roland Schmitt*- Hannover Medical School, Hanover, Germany
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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-cell-mediated clearance of senescent epithelial cells can be an important factor for the maintenance of kidney function. In this study, we have established a model to directly monitor natural killer (NK) cell-mediated clearance of senescent renal tubular epithelial cells. 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.
Keywords: senescence, NK cells, Kidney, PTEC, CKD - chronic kidney disease, Immunosurveilance, Immune System
Received: 20 Mar 2025; Accepted: 17 Jun 2025.
Copyright: © 2025 Funk, Sinning, Soerensen-Zender, Wulfmeyer, Schmidt-Ott, Brand, Halle and Schmitt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Stephan Halle, Hannover Medical School, Hanover, Germany
Roland Schmitt, Hannover Medical School, Hanover, Germany
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