Senescence-induced endothelial phenotypes underpin immune-mediated senescence surveillance Article Swipe
Kelvin Yin
,
Daniel A. Patten
,
Sarah Gough
,
Susana de Barros Gonçalves
,
Adelyne Chan
,
Ioana Olan
,
Liam D. Cassidy
,
Marta Poblocka
,
Haoran Zhu
,
Aaron T. L. Lun
,
Martijn J. Schuijs
,
Andrew Young
,
Celia Pilar Martinez‐Jimenez
,
Timotheus Y.F. Halim
,
Shishir Shetty
,
Masashi Narita
,
Matthew Hoare
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/gad.349585.122
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/gad.349585.122
Senescence is a stress-responsive tumor suppressor mechanism associated with expression of the senescence-associated secretory phenotype (SASP). Through the SASP, senescent cells trigger their own immune-mediated elimination, which if evaded leads to tumorigenesis. Senescent parenchymal cells are separated from circulating immunocytes by the endothelium, which is targeted by microenvironmental signaling. Here we show that SASP induces endothelial cell NF-κB activity and that SASP-induced endothelial expression of the canonical NF-κB component Rela underpins senescence surveillance. Using human liver sinusoidal endothelial cells (LSECs), we show that SASP-induced endothelial NF-κB activity regulates a conserved transcriptional program supporting immunocyte recruitment. Furthermore, oncogenic hepatocyte senescence drives murine LSEC NF-κB activity in vivo. Critically, we show two distinct endothelial pathways in senescence surveillance. First, endothelial-specific loss of Rela prevents development of Stat1-expressing CD4 + T lymphocytes. Second, the SASP up-regulates ICOSLG on LSECs, with the ICOS–ICOSLG axis contributing to senescence cell clearance. Our results show that the endothelium is a nonautonomous SASP target and an organizing center for immune-mediated senescence surveillance.
Related Topics
Concepts
Biology
Senescence
Phenotype
Cellular senescence
Immune system
Immune surveillance
Cell biology
Genetics
Immunology
Gene
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1101/gad.349585.122
- http://genesdev.cshlp.org/content/36/9-10/533.full.pdf
- OA Status
- diamond
- Cited By
- 55
- References
- 48
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4281560563
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4281560563Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/gad.349585.122Digital Object Identifier
- Title
-
Senescence-induced endothelial phenotypes underpin immune-mediated senescence surveillanceWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-05-01Full publication date if available
- Authors
-
Kelvin Yin, Daniel A. Patten, Sarah Gough, Susana de Barros Gonçalves, Adelyne Chan, Ioana Olan, Liam D. Cassidy, Marta Poblocka, Haoran Zhu, Aaron T. L. Lun, Martijn J. Schuijs, Andrew Young, Celia Pilar Martinez‐Jimenez, Timotheus Y.F. Halim, Shishir Shetty, Masashi Narita, Matthew HoareList of authors in order
- Landing page
-
https://doi.org/10.1101/gad.349585.122Publisher landing page
- PDF URL
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https://genesdev.cshlp.org/content/36/9-10/533.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
diamondOpen access status per OpenAlex
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https://genesdev.cshlp.org/content/36/9-10/533.full.pdfDirect OA link when available
- Concepts
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Biology, Senescence, Phenotype, Cellular senescence, Immune system, Immune surveillance, Cell biology, Genetics, Immunology, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
55Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 23, 2024: 21, 2023: 9, 2022: 2Per-year citation counts (last 5 years)
- References (count)
-
48Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.surveillance. | 72, 115, 163 |
| abstract_inverted_index.tumorigenesis. | 31 |
| abstract_inverted_index.immune-mediated | 24, 161 |
| abstract_inverted_index.transcriptional | 90 |
| abstract_inverted_index.Stat1-expressing | 124 |
| abstract_inverted_index.stress-responsive | 3 |
| abstract_inverted_index.microenvironmental | 47 |
| abstract_inverted_index.endothelial-specific | 117 |
| abstract_inverted_index.senescence-associated | 12 |
| cited_by_percentile_year.max | 100 |
| cited_by_percentile_year.min | 94 |
| countries_distinct_count | 3 |
| institutions_distinct_count | 17 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.6600000262260437 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.97944883 |
| citation_normalized_percentile.is_in_top_1_percent | True |
| citation_normalized_percentile.is_in_top_10_percent | True |