Physical Sciences and Mathematics Commons^™

Activation Of Trpa1 Nociceptor Promotes Systemic Adult Mammalian Skin Regeneration, Jenny J. Wei, Hali S. Kim, Casey A. Spencer, Donna Brennan-Crispi, Ying Zheng, Nicolette M. Johnson, Misha Rosenbach, Christopher Miller, Denis H. Y. Leung, George Cotsarelis, Thomas H. Leung

Research Collection School Of Economics

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 …