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; 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

Jin Han, Christopher Cherry, Joscelyn C. Mejías, Kavita Krishnan, Anna Ruta, David R. Maestas, 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

School of Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	2310476
Journal	Advanced Materials
Volume	36
Issue number	43
DOIs	https://doi.org/10.1002/adma.202310476
State	Published - Oct 24 2024

Keywords

aging
biomaterials
senescence
tissue engineering

ASJC Scopus subject areas

General Materials Science
Mechanics of Materials
Mechanical Engineering

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10.1002/adma.202310476

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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. (2024). Age-associated Senescent – T Cell Signaling Promotes Type 3 Immunity that Inhibits the Biomaterial Regenerative Response. Advanced Materials, 36(43), Article 2310476. https://doi.org/10.1002/adma.202310476

Han, J, Cherry, C, Mejías, JC, Krishnan, K, Ruta, A, Maestas, DR, Peña, AN, Nguyen, HH, Nagaraj, S, Yang, B, Gray-Gaillard, EF, Rutkowski, N, Browne, M, Tam, AJ, Fertig, EJ, Housseau, F, Ganguly, S, Moore, EM, Pardoll, DM & Elisseeff, JH 2024, 'Age-associated Senescent – T Cell Signaling Promotes Type 3 Immunity that Inhibits the Biomaterial Regenerative Response', Advanced Materials, vol. 36, no. 43, 2310476. https://doi.org/10.1002/adma.202310476

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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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AU - Cherry, Christopher

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AU - Krishnan, Kavita

AU - Ruta, Anna

AU - Maestas, David R.

AU - Peña, Alexis N.

AU - Nguyen, Helen Hieu

AU - Nagaraj, Sushma

AU - Yang, Brenda

AU - Gray-Gaillard, Elise F.

AU - Rutkowski, Natalie

AU - Browne, Maria

AU - Tam, Ada J.

AU - Fertig, Elana J.

AU - Housseau, Franck

AU - Ganguly, Sudipto

AU - Moore, Erika M.

AU - Pardoll, Drew M.

AU - Elisseeff, Jennifer H.

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

Abstract

Keywords

ASJC Scopus subject areas

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