Activation of TRPA1 nociceptor promotes systemic adult mammalian skin regeneration

Author

Jenny J. WEI, University of Pennsylvania
Hali S. KIM, University of Pennsylvania
Casey A. SPENCER, University of Pennsylvania
Donna BRENNAN-CRISPI, University of Pennsylvania
Ying ZHENG, University of Pennsylvania
Nicolette M. JOHNSON, University of Pennsylvania
Misha ROSENBACH, University of Pennsylvania
Christopher MILLER, University of Pennsylvania
Denis H. Y. LEUNG, Singapore Management UniversityFollow
George COTSARELIS, University of Pennsylvania
Thomas H. LEUNG, University of Pennsylvania

Publication Type

Journal Article

Version

acceptedVersion

Publication Date

8-2020

Abstract

Adult mammalian wounds, with rare exception, heal with fibrotic scars that severely disrupt tissue architecture and function. Regenerative medicine seeks methods to avoid scar formation and restore the original tissue structures. We show in three adult mouse models that pharmacologic activation of the nociceptor TRPA1 on cutaneous sensory neurons reduces scar formation and can also promote tissue regeneration. Local activation of TRPA1 induces tissue regeneration on distant untreated areas of injury, demonstrating a systemic effect. Activated TRPA1 stimulates local production of interleukin-23 (IL-23) by dermal dendritic cells, leading to activation of circulating dermal IL-17–producing γδ T cells. Genetic ablation of TRPA1, IL-23, dermal dendritic cells, or γδ T cells prevents TRPA1-mediated tissue regeneration. These results reveal a cutaneous neuroimmune-regeneration cascade triggered by topical TRPA1 activators that promotes adult mammalian tissue regeneration, presenting a new avenue for research and development of therapies for wounds and scars.

Discipline

Biostatistics | Econometrics | Medicine and Health Sciences

Research Areas

Econometrics

Publication

Science Immuology

Volume

5

Issue

50

First Page

1

Last Page

18

ISSN

2470-9468

Identifier

10.1126/sciimmunol.aba5683

Publisher

AAAS

Embargo Period

7-14-2021

Citation

WEI, Jenny J.; KIM, Hali S.; SPENCER, Casey A.; BRENNAN-CRISPI, Donna; ZHENG, Ying; JOHNSON, Nicolette M.; ROSENBACH, Misha; MILLER, Christopher; LEUNG, Denis H. Y.; COTSARELIS, George; and LEUNG, Thomas H.. Activation of TRPA1 nociceptor promotes systemic adult mammalian skin regeneration. (2020). Science Immuology. 5, (50), 1-18.
Available at: https://ink.library.smu.edu.sg/soe_research/2483

Copyright Owner and License

Authors

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Additional URL

https://doi.org/10.1126/sciimmunol.aba5683