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Selective Elimination of Senescent Fibroblasts by Targeting the Cell Surface Protein ACKR3
The accumulation of senescent cells in aging tissues is associated with age-related diseases and functional decline. Thus, senolysis, a therapy aimed at rejuvenation by removing senescent cells from the body, is being developed. However, this therapy requires the identification of membrane surface a...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9223754/ https://www.ncbi.nlm.nih.gov/pubmed/35742971 http://dx.doi.org/10.3390/ijms23126531 |
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author | Takaya, Kento Asou, Toru Kishi, Kazuo |
author_facet | Takaya, Kento Asou, Toru Kishi, Kazuo |
author_sort | Takaya, Kento |
collection | PubMed |
description | The accumulation of senescent cells in aging tissues is associated with age-related diseases and functional decline. Thus, senolysis, a therapy aimed at rejuvenation by removing senescent cells from the body, is being developed. However, this therapy requires the identification of membrane surface antigens that are specifically expressed on senescent cells for their selective elimination. We showed that atypical chemokine receptor 3 (ACKR3), a receptor of the CXC motif chemokine 12 (CXCL12) implicated in cancer, inflammation, and cardiovascular disorders, is selectively expressed on the surface of senescent human fibroblasts but not on proliferating cells. Importantly, the differential presence of ACKR3 enabled the isolation of senescent cells by flow cytometry using anti-ACKR3 antibodies. Furthermore, antibody-dependent cellular cytotoxicity assays revealed that cell surface ACKR3 preferentially sensitizes senescent but not dividing fibroblasts to cell injury by natural killer cells. Conclusively, the selective expression of ACKR3 on the surface of senescent cells allows the preferential elimination of senescent cells. These results might contribute to the future development of novel senolysis approaches. |
format | Online Article Text |
id | pubmed-9223754 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92237542022-06-24 Selective Elimination of Senescent Fibroblasts by Targeting the Cell Surface Protein ACKR3 Takaya, Kento Asou, Toru Kishi, Kazuo Int J Mol Sci Article The accumulation of senescent cells in aging tissues is associated with age-related diseases and functional decline. Thus, senolysis, a therapy aimed at rejuvenation by removing senescent cells from the body, is being developed. However, this therapy requires the identification of membrane surface antigens that are specifically expressed on senescent cells for their selective elimination. We showed that atypical chemokine receptor 3 (ACKR3), a receptor of the CXC motif chemokine 12 (CXCL12) implicated in cancer, inflammation, and cardiovascular disorders, is selectively expressed on the surface of senescent human fibroblasts but not on proliferating cells. Importantly, the differential presence of ACKR3 enabled the isolation of senescent cells by flow cytometry using anti-ACKR3 antibodies. Furthermore, antibody-dependent cellular cytotoxicity assays revealed that cell surface ACKR3 preferentially sensitizes senescent but not dividing fibroblasts to cell injury by natural killer cells. Conclusively, the selective expression of ACKR3 on the surface of senescent cells allows the preferential elimination of senescent cells. These results might contribute to the future development of novel senolysis approaches. MDPI 2022-06-10 /pmc/articles/PMC9223754/ /pubmed/35742971 http://dx.doi.org/10.3390/ijms23126531 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Takaya, Kento Asou, Toru Kishi, Kazuo Selective Elimination of Senescent Fibroblasts by Targeting the Cell Surface Protein ACKR3 |
title | Selective Elimination of Senescent Fibroblasts by Targeting the Cell Surface Protein ACKR3 |
title_full | Selective Elimination of Senescent Fibroblasts by Targeting the Cell Surface Protein ACKR3 |
title_fullStr | Selective Elimination of Senescent Fibroblasts by Targeting the Cell Surface Protein ACKR3 |
title_full_unstemmed | Selective Elimination of Senescent Fibroblasts by Targeting the Cell Surface Protein ACKR3 |
title_short | Selective Elimination of Senescent Fibroblasts by Targeting the Cell Surface Protein ACKR3 |
title_sort | selective elimination of senescent fibroblasts by targeting the cell surface protein ackr3 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9223754/ https://www.ncbi.nlm.nih.gov/pubmed/35742971 http://dx.doi.org/10.3390/ijms23126531 |
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