Department of Plastic and Reconstructive Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.
Int J Mol Sci. 2022 Jun 10;23(12):6531. doi: 10.3390/ijms23126531.
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.
衰老细胞在衰老组织中的积累与年龄相关的疾病和功能下降有关。因此，正在开发一种旨在通过从体内清除衰老细胞来实现年轻化的疗法，即衰老细胞消除疗法。然而，这种疗法需要鉴定在衰老细胞表面特异性表达的膜表面抗原，以便对其进行选择性消除。我们发现，非典型趋化因子受体 3（ACKR3）是一种与癌症、炎症和心血管疾病有关的 CXC 基序趋化因子 12（CXCL12）的受体，它选择性地表现在衰老的人成纤维细胞表面，但不在增殖细胞上。重要的是，ACKR3 的差异表达使得可以使用抗 ACKR3 抗体通过流式细胞术分离衰老细胞。此外，抗体依赖性细胞毒性测定显示，细胞表面 ACKR3 优先使衰老但不是分裂的成纤维细胞对自然杀伤细胞的细胞损伤敏感。总之，衰老细胞表面选择性表达 ACKR3 允许优先消除衰老细胞。这些结果可能有助于未来开发新的衰老细胞消除方法。
