dsRNA Released by Tissue Damage Activates TLR3 to Drive Skin Regeneration

Amanda M. Nelson, Sashank K. Reddy, Tabetha S. Ratliff, M. Zulfiquer Hossain, Adiya S. Katseff, Amadeus S. Zhu, Emily Chang, Sydney R. Resnik, Carly Page, Dongwon Kim, Alexander J. Whittam, Lloyd S. Miller, Luis A. Garza

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Summary Regeneration of skin and hair follicles after wounding - a process known as wound-induced hair neogenesis (WIHN) - is a rare example of adult organogenesis in mammals. As such, WIHN provides a unique model system for deciphering mechanisms underlying mammalian regeneration. Here, we show that dsRNA, which is released from damaged skin, activates Toll-Like Receptor 3 (TLR3) and its downstream effectors IL-6 and STAT3 to promote hair follicle regeneration. Conversely, TLR3-deficient animals fail to initiate WIHN. TLR3 activation promotes expression of hair follicle stem cell markers and induces elements of the core hair morphogenetic program, including ectodysplasin A receptor (EDAR) and the Wnt and Shh pathways. Our results therefore show that dsRNA and TLR3 link the earliest events of mammalian skin wounding to regeneration and suggest potential therapeutic approaches for promoting hair neogenesis.

Original languageEnglish (US)
Article number1812
Pages (from-to)139-151
Number of pages13
JournalCell Stem Cell
Volume17
Issue number2
DOIs
StatePublished - Aug 6 2015

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Cell Biology

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    Nelson, A. M., Reddy, S. K., Ratliff, T. S., Hossain, M. Z., Katseff, A. S., Zhu, A. S., Chang, E., Resnik, S. R., Page, C., Kim, D., Whittam, A. J., Miller, L. S., & Garza, L. A. (2015). dsRNA Released by Tissue Damage Activates TLR3 to Drive Skin Regeneration. Cell Stem Cell, 17(2), 139-151. [1812]. https://doi.org/10.1016/j.stem.2015.07.008