Mechanisms of natural killer cell-mediated clearance of senescent renal tubular epithelial cells
IntroductionIntact 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. Therefo...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-06-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1597230/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850110746487160832 |
|---|---|
| author | Nils David Funk Julius Sinning Patrick Schaser Patrick Schaser Inga Soerensen-Zender Vera Christine Wulfmeyer Kai Schmidt-Ott Korbinian Brand Stephan Halle Stephan Halle Roland Schmitt Roland Schmitt |
| author_facet | Nils David Funk Julius Sinning Patrick Schaser Patrick Schaser Inga Soerensen-Zender Vera Christine Wulfmeyer Kai Schmidt-Ott Korbinian Brand Stephan Halle Stephan Halle Roland Schmitt Roland Schmitt |
| author_sort | Nils David Funk |
| collection | DOAJ |
| description | IntroductionIntact 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.MethodsIn 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 DiscussionWe 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. |
| format | Article |
| id | doaj-art-a626fbada02e458d8e416178787e0a9f |
| institution | OA Journals |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-a626fbada02e458d8e416178787e0a9f2025-08-20T02:37:46ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-06-011310.3389/fcell.2025.15972301597230Mechanisms of natural killer cell-mediated clearance of senescent renal tubular epithelial cellsNils David Funk0Julius Sinning1Patrick Schaser2Patrick Schaser3Inga Soerensen-Zender4Vera Christine Wulfmeyer5Kai Schmidt-Ott6Korbinian Brand7Stephan Halle8Stephan Halle9Roland Schmitt10Roland Schmitt11Department of Nephrology and Hypertension, Hannover Medical School, Hannover, GermanyDepartment of Nephrology and Hypertension, Hannover Medical School, Hannover, GermanyInstitute of Clinical Chemistry and Laboratory Medicine, Hannover Medical School, Hannover, GermanyInstitute of Immunology, Hannover Medical School, Hannover, GermanyDepartment of Nephrology and Hypertension, Hannover Medical School, Hannover, GermanyDepartment of Nephrology and Hypertension, Hannover Medical School, Hannover, GermanyDepartment of Nephrology and Hypertension, Hannover Medical School, Hannover, GermanyInstitute of Clinical Chemistry and Laboratory Medicine, Hannover Medical School, Hannover, GermanyInstitute of Clinical Chemistry and Laboratory Medicine, Hannover Medical School, Hannover, GermanyInstitute of Immunology, Hannover Medical School, Hannover, GermanyDepartment of Nephrology and Hypertension, Hannover Medical School, Hannover, GermanyDepartment of Nephrology and Hypertension, University Hospital Schleswig-Holstein, Kiel, GermanyIntroductionIntact 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.MethodsIn 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 DiscussionWe 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.https://www.frontiersin.org/articles/10.3389/fcell.2025.1597230/fullsenescenceNK cellskidneyPTECCKD - chronic kidney diseaseimmunosurveillance |
| spellingShingle | Nils David Funk Julius Sinning Patrick Schaser Patrick Schaser Inga Soerensen-Zender Vera Christine Wulfmeyer Kai Schmidt-Ott Korbinian Brand Stephan Halle Stephan Halle Roland Schmitt Roland Schmitt Mechanisms of natural killer cell-mediated clearance of senescent renal tubular epithelial cells Frontiers in Cell and Developmental Biology senescence NK cells kidney PTEC CKD - chronic kidney disease immunosurveillance |
| title | Mechanisms of natural killer cell-mediated clearance of senescent renal tubular epithelial cells |
| title_full | Mechanisms of natural killer cell-mediated clearance of senescent renal tubular epithelial cells |
| title_fullStr | Mechanisms of natural killer cell-mediated clearance of senescent renal tubular epithelial cells |
| title_full_unstemmed | Mechanisms of natural killer cell-mediated clearance of senescent renal tubular epithelial cells |
| title_short | Mechanisms of natural killer cell-mediated clearance of senescent renal tubular epithelial cells |
| title_sort | mechanisms of natural killer cell mediated clearance of senescent renal tubular epithelial cells |
| topic | senescence NK cells kidney PTEC CKD - chronic kidney disease immunosurveillance |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1597230/full |
| work_keys_str_mv | AT nilsdavidfunk mechanismsofnaturalkillercellmediatedclearanceofsenescentrenaltubularepithelialcells AT juliussinning mechanismsofnaturalkillercellmediatedclearanceofsenescentrenaltubularepithelialcells AT patrickschaser mechanismsofnaturalkillercellmediatedclearanceofsenescentrenaltubularepithelialcells AT patrickschaser mechanismsofnaturalkillercellmediatedclearanceofsenescentrenaltubularepithelialcells AT ingasoerensenzender mechanismsofnaturalkillercellmediatedclearanceofsenescentrenaltubularepithelialcells AT verachristinewulfmeyer mechanismsofnaturalkillercellmediatedclearanceofsenescentrenaltubularepithelialcells AT kaischmidtott mechanismsofnaturalkillercellmediatedclearanceofsenescentrenaltubularepithelialcells AT korbinianbrand mechanismsofnaturalkillercellmediatedclearanceofsenescentrenaltubularepithelialcells AT stephanhalle mechanismsofnaturalkillercellmediatedclearanceofsenescentrenaltubularepithelialcells AT stephanhalle mechanismsofnaturalkillercellmediatedclearanceofsenescentrenaltubularepithelialcells AT rolandschmitt mechanismsofnaturalkillercellmediatedclearanceofsenescentrenaltubularepithelialcells AT rolandschmitt mechanismsofnaturalkillercellmediatedclearanceofsenescentrenaltubularepithelialcells |