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Cited by 17Tissue Engineering and Regenerative MedicineWound Healing and TreatmentsT-cell and B-cell Immunology

Age‐associated Senescent – T Cell Signaling Promotes Type 3 Immunity that Inhibits the Biomaterial Regenerative Response

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Han, Jin, Cherry, Christopher, Mejías, Joscelyn C., Krishnan, Kavita, Ruta, Anna, Maestas, David R., Peña, Alexis N., Nguyen, Helen Hieu +12 more·2024·Advanced Materials
DOI 10.1002/adma.202310476PMC PMC12522171
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Abstract

Aging is associated with immunological changes that compromise response to infections and vaccines, exacerbate inflammatory diseases and can potentially mitigate tissue repair. Even so, age-related changes to the immune response to tissue damage and regenerative medicine therapies remain unknown. Here, it is characterized how aging induces changes in immunological signatures that inhibit tissue repair and therapeutic response to a clinical regenerative biological scaffold derived from extracellular matrix. Signatures of inflammation and interleukin (IL)-17 signaling increased with injury and treatment both locally and regionally in aged animals, and computational analysis uncovered age-associated senescent-T cell communication that promotes type 3 immunity in T cells. Local inhibition of type 3 immune activation using IL17-neutralizing antibodies improves healing and restores therapeutic response to the regenerative biomaterial, promoting muscle repair in older animals. These results provide insights into tissue immune dysregulation that occurs with aging that can be targeted to rejuvenate repair.

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  • More prominent activation of the Th17 response in aged individuals is a main driver of age-related differences in response to ECM bioscaffolds.

    “This and a previous study [172] point towards the more prominent activation of the Th17 response in aged individuals as a main driver of such differences.”

    From Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review (2025) · cites this paper as [172]

    The Results sections on aging and systemic type 3 immunity report stronger IL17/Th17-associated responses to ECM treatment in aged mice and suggest these responses may contribute to reduced regeneration. The combination-therapy Results show improved repair when IL17 is neutralized. But the paper studies mice, not aged people, and does not establish Th17 activation as the main driver of the age-related differences. (LLM, conf=0.84)

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Authors
Han, J., Cherry, C., Mejías, J. C., Krishnan, K., Ruta, A., Maestas, D. R., Peña, A. N., Nguyen, H. H., Nagaraj, S., Yang, B., Gray‐Gaillard, E. F., Rutkowski, N., Browne, M., Tam, A. J., Fertig, E. J., Housseau, F., Ganguly, S., Moore, E. M., Pardoll, D. M., & Elisseeff, J. H.
Affiliations
  • Johns Hopkins University (US)
  • Translational Tissue Engineering Center Wilmer Eye Institute and Department of Biomedical Engineering Johns Hopkins University Baltimore MD 21231 USA
  • University of Florida (US)
Corresponding author
Elisseeff, Jennifer H.
ORCID
Venue
Advanced Materials
Publisher
Wiley
Published
2023-12-28
Volume
36
Issue
43
Pages
e2310476-e2310476
ISSN
  • 0935-9648 (ISSN-L)
  • 1521-4095
DOI
10.1002/adma.202310476
PMC
PMC12522171
OpenAlex
W4389683686
Cited by
17
References
8
Citations by year
2026: 4 · 2025: 11 · 2024: 2
FWCI
4.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Advanced Materials (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion, cc-by-nc-nd)
Funders
National Institutes of Health (DP1AR076959, R01AG063801)
Topics
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
immunosenescence, senescent T cells, type 3 immunity, IL-17 signaling, aging, tissue repair, regenerative biomaterials, extracellular matrix scaffolds, muscle repair, inflammation
MeSH terms
Aging, Animals, Biocompatible Materials, Extracellular Matrix, Mice, Inbred C57BL, Regeneration, T-Lymphocytes, Wound Healing, Signal Transduction, Cellular Senescence, Interleukin-17, Regenerative Medicine, Mice, Tissue Scaffolds

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