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Publication : dsRNA Released by Tissue Damage Activates TLR3 to Drive Skin Regeneration.

First Author  Nelson AM Year  2015
Journal  Cell Stem Cell Volume  17
Issue  2 Pages  139-51
PubMed ID  26253200 Mgi Jnum  J:315930
Mgi Id  MGI:6829259 Doi  10.1016/j.stem.2015.07.008
Citation  Nelson AM, et al. (2015) dsRNA Released by Tissue Damage Activates TLR3 to Drive Skin Regeneration. Cell Stem Cell 17(2):139-51
abstractText  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.
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