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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...

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Detalles Bibliográficos
Autores principales: Takaya, Kento, Asou, Toru, Kishi, Kazuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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