Invariant natural killer T cells coordinate removal of senescent cells
Open accessAbstract
BACKGROUND: The failure of immune surveillance to remove senescent cells drive age-related diseases. Here, we target an endogenous immune surveillance mechanism that can promote elimination of senescent cells and reverse disease progression. METHODS: We identify a class of lipid-activated T cells, invariant natural killer T cells (iNKTs) are involved in the removal of pathologic senescent cells. We use two disease models in which senescent cells accumulate to test whether activation of iNKT cells was sufficient to eliminate senescent cells in vivo. FINDINGS: Senescent preadipocytes accumulate in white adipose tissue of chronic high-fat diet (HFD) fed mice, and activation of iNKT cells with the prototypical glycolipid antigen alpha-galactosylceramide (αGalCer) led to a reduction of these cells with improved glucose control. Similarly, senescent cells accumulate within the lungs of mice injured by inhalational bleomycin, and αGalCer-induced activation of iNKT cells greatly limited this accumulation, decreased the lung fibrosis and improved survival. Furthermore, co-culture experiments showed that the preferential cytotoxic activity of iNKT cells to senescent cells is conserved in human cells. CONCLUSIONS: These results uncover a senolytic capacity of tissue-resident iNKT cells and pave the way for anti-senescence therapies that target these cells and their mechanism of activation.
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Senescent cells are at least in part cleared by cells of both the innate and adaptive immune systems if such clearing function is not compromised.
“More specifically, senescent cells are, at least in part, cleared by cells of both the innate and adaptive immune systems76,173–175 if such clearing function is not compromised, which remains to be studied in greater detail in the context of COVID-19 (ref.176).”
From COVID-19 and cellular senescence (2023) · cites this paper as [175]
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- Authors
- Arora, S., Thompson, P. J., Wang, Y., Bhattacharyya, A., Apostolopoulou, H., Hatano, R., Naikawadi, R. P., Shah, A., Wolters, P. J., Koliwad, S., Bhattacharya, M., & Bhushan, A.
- Affiliations
- University of California, San Francisco (US)
- MBC BioLabs (United States) (US)
- Corresponding author
- Bhushan, Anil
- ORCID
- Venue
- Med
- Publisher
- Elsevier BV
- Published
- 2021-08
- Volume
- 2
- Issue
- 8
- Pages
- 938-950.e8
- ISSN
- 2666-6340 (ISSN-L)
- PMC
- PMC8491998
- OpenAlex
- W3160798261
- Cited by
- 77
- References
- 40
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 19 · 2023: 15 · 2022: 12 · 2021: 2
- FWCI
- 7.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Med (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- University of California, San Francisco
- National Institutes of Health (R01DK118099, R01DK121794)
- Larry L. Hillblom Foundation
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- invariant natural killer T cells, senescent cells, immune surveillance, alpha-galactosylceramide, preadipocytes, white adipose tissue, high-fat diet, bleomycin-induced lung injury, pulmonary fibrosis, glycemic control, anti-senescence therapy, age-related diseases
- MeSH terms
- Animals, Cellular Senescence, Lymphocyte Count, Mice, Natural Killer T-Cells, Diet, High-Fat
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