Hypothesis: Wound-induced TLR3 activation stimulates endogenous retinoic acid synthesis and signalling during regeneration.

Although the mechanism is unclear, it has been shown that genetically normal adult mice with a large wound form de novo morphogenesis of hair follicles in wound-induced hair neogenesis (WIHN)(1). We focused on how tissues recognize damage signals and identified that double-stranded RNA (dsRNA)-mediated toll-like receptor 3 (TLR3) activation stimulates WIHN. Here, we propose a hypothesis that TLR3 stimulates retinoic acid synthesis and signalling to allow for regeneration, suggesting that common clinical methods of facial rejuvenation in human subjects through damage (such as lasers or dermabrasion), and the use of topical retinoids reflect the same biologic pathway.