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

Jin Han; Christopher Cherry; Joscelyn C Mejías; Kavita Krishnan; Anna Ruta; David R Maestas Jr; Alexis N Peña; Helen Hieu Nguyen; Sushma Nagaraj; Brenda Yang; Elise F Gray-Gaillard; Natalie Rutkowski; Maria Browne; Ada J Tam; Elana J Fertig; Franck Housseau; Sudipto Ganguly; Erika M Moore; Drew M Pardoll; Jennifer H Elisseeff

doi:10.1002/adma.202310476

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

Adv Mater. 2023 Dec 12:e2310476. doi: 10.1002/adma.202310476. Online ahead of print.

Authors

Jin Han¹, Christopher Cherry¹, Joscelyn C Mejías¹, Kavita Krishnan¹, Anna Ruta¹, David R Maestas Jr¹, Alexis N Peña¹, Helen Hieu Nguyen¹, Sushma Nagaraj², Brenda Yang¹, Elise F Gray-Gaillard¹, Natalie Rutkowski¹, Maria Browne¹, Ada J Tam³, Elana J Fertig^{4

5

6}, Franck Housseau³, Sudipto Ganguly³, Erika M Moore⁷, Drew M Pardoll³, Jennifer H Elisseeff^{1

3}

Affiliations

¹ Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
² Department of Neurology, Brain Science Institute, Johns Hopkins University, Baltimore, MD, 21231, USA.
³ Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
⁴ Department of Biomedical Engineering and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA.
⁵ Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
⁶ Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, 21218, USA.
⁷ Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.

PMID: 38087458
DOI: 10.1002/adma.202310476

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.

Keywords: aging; biomaterials; senescence; tissue engineering.

Abstract

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