Recruitment of inflammatory monocytes by senescent fibroblasts inhibits antigen-specific tissue immunity during human aging
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Abstract
We have previously shown that healthy older adults exhibit reduced cutaneous immune responses during a varicella zoster virus (VZV) antigen challenge that correlated with a nonspecific inflammatory response to the injection itself. Here we found that needle damage during intradermal injections in older adults led to an increase in the number of cutaneous senescent fibroblasts expressing CCL2, resulting in the local recruitment of inflammatory monocytes. These infiltrating monocytes secreted prostaglandin E2, which inhibited resident memory T cell activation and proliferation. Pretreatment of older participants with a p38 mitogen-activated protein kinase inhibitor in vivo decreased CCL2 expression and inhibited monocyte recruitment and secretion of prostaglandin E2. This coincided with an increased response to VZV antigen challenge in the skin. Our results point to a series of molecular and cellular mechanisms that link cellular senescence, tissue damage, excessive inflammation and reduced immune responsiveness in human skin and demonstrate that tissue-specific immunity can be restored in older adults by short-term inhibition of inflammatory responses.
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Senescent fibroblasts in aged skin recruit proinflammatory monocytes by secreting MCP-1.
“Additionally, senescent fibroblasts in aged skin recruit proinflammatory monocytes by secreting MCP-1 (48).”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [48]
SASP factors may blunt T cell responses in aged individuals by promoting the secretion of T cell-suppressing prostaglandin E2 (PGE2), implicating the SASP in the age-related decline of adaptive immunity.
“SASP factors may also blunt T cell responses in aged individuals by promoting the secretion of T cell–suppressing prostaglandin E2 (PGE2), implicating the SASP in the age-related decline of adaptive immunity (48).”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [48]
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- Authors
- Chambers, E. S., Vukmanovic-Stejic, M., Shih, B. B., Trahair, H., Subramanian, P., Devine, O. P., Glanville, J., Gilroy, D., Rustin, M. H. A., Freeman, T. C., Mabbott, N. A., & Akbar, A. N.
- Affiliations
- Queen Mary University of London (GB)
- Roslin Institute (GB)
- University College London (GB)
- The Royal Free Hospital (GB)
- Corresponding author
- Akbar, Arne N.
- ORCID
- Venue
- Nature Aging
- Published
- 2021-01-14
- Volume
- 1
- Issue
- 1
- Pages
- 101-113
- ISSN
- 2662-8465 (ISSN-L)
- OpenAlex
- W3118863695
- Cited by
- 96
- References
- 51
- Citations by year
- 2026: 17 · 2025: 22 · 2024: 17 · 2023: 12 · 2022: 14 · 2021: 9 · 2020: 5
- FWCI
- 8.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Aging (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Lancaster EPrints (Lancaster University) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- Funders
- RCUK | Medical Research Council (G0901102, MR/M003833/1, MR/T030534/1)
- RCUK | Biotechnology and Biological Sciences Research Council (BBS/E/D/20002173)
- British Skin Foundation (BSF5012)
- Dermatrust
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- cellular senescence, senescent fibroblasts, inflammatory monocytes, MCP-1, prostaglandin E2, tissue-resident memory T cells, skin immunity, varicella-zoster virus, aging, p38 MAPK inhibition, intradermal injection, skin inflammation, immunosenescence
- MeSH terms
- Aged, Aging, Fibroblasts, Humans, Lymphocyte Activation, Monocytes, Herpesvirus 3, Human, Dinoprostone
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