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Age-associated Senescent - T Cell Signaling Promotes Type 3 Immunity that Inhibits the Biomaterial Regenerative Response.
Han, Jin; Cherry, Christopher; Mejías, Joscelyn C; Krishnan, Kavita; Ruta, Anna; Maestas, David R; Peña, Alexis N; Nguyen, Helen Hieu; Nagaraj, Sushma; Yang, Brenda; Gray-Gaillard, Elise F; Rutkowski, Natalie; Browne, Maria; Tam, Ada J; Fertig, Elana J; Housseau, Franck; Ganguly, Sudipto; Moore, Erika M; Pardoll, Drew M; Elisseeff, Jennifer H.
Afiliação
  • Han J; Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
  • Cherry C; Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
  • Mejías JC; Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
  • Krishnan K; Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
  • Ruta A; Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
  • Maestas DR; Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
  • Peña AN; Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
  • Nguyen HH; Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
  • Nagaraj S; Department of Neurology, Brain Science Institute, Johns Hopkins University, Baltimore, MD, 21231, USA.
  • Yang B; Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
  • Gray-Gaillard EF; Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
  • Rutkowski N; Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
  • Browne M; Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21231, USA.
  • Tam AJ; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
  • Fertig EJ; Department of Biomedical Engineering and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA.
  • Housseau F; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
  • Ganguly S; Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, 21218, USA.
  • Moore EM; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
  • Pardoll DM; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
  • Elisseeff JH; Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
Adv Mater ; : e2310476, 2023 Dec 12.
Article em En | MEDLINE | ID: mdl-38087458
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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Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Adv Mater Assunto da revista: BIOFISICA / QUIMICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Adv Mater Assunto da revista: BIOFISICA / QUIMICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos