Identification of senescent cell surface targetable protein DPP4
- Kyoung Mi Kim1,4,
- Ji Heon Noh1,4,
- Monica Bodogai1,
- Jennifer L. Martindale1,
- Xiaoling Yang1,
- Fred E. Indig1,
- Sandip K. Basu2,
- Kei Ohnuma3,
- Chikao Morimoto3,
- Peter F. Johnson2,
- Arya Biragyn1,
- Kotb Abdelmohsen1 and
- Myriam Gorospe1
- 1National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA;
- 2National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA;
- 3Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan
- Corresponding author: kyoungmi.kim{at}nih.gov
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↵4 These authors contributed equally to this work.
Abstract
Senescent cell accumulation in aging tissues is linked to age-associated diseases and declining function, prompting efforts to eliminate them. Mass spectrometry analysis revealed that DPP4 (dipeptidyl peptidase 4) was selectively expressed on the surface of senescent, but not proliferating, human diploid fibroblasts. Importantly, the differential presence of DPP4 allowed flow cytometry-mediated isolation of senescent cells using anti-DPP4 antibodies. Moreover, antibody-dependent cell-mediated cytotoxicity (ADCC) assays revealed that the cell surface DPP4 preferentially sensitized senescent, but not dividing, fibroblasts to cytotoxicity by natural killer cells. In sum, the selective expression of DPP4 on the surface of senescent cells enables their preferential elimination.
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Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.302570.117.
- Received May 24, 2017.
- Accepted August 2, 2017.
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