Toward Understanding Wound Immunology for High-Fidelity Skin Regeneration

Effective tissue repair is vital for the survival of organisms. Yet, how the immune system coordinates with tissue stem cells (SCs) to effect postnatal tissue restoration remains elusive. This review presents current knowledge surrounding wound-induced SC and immune signaling that favors tissue repair, including wound healing and regeneration. We discuss factors that affect regenerative capacities among organisms and the dynamics of local immune cells and SCs during reepithelialization. We also present recent insights into how immune niches communicate with SCs or other body systems to restore the epithelial architecture. Additionally, we summarize our findings on functional wound regeneration, specifically how alarmin (double-stranded RNA [dsRNA])-activated Toll-like receptor signaling and host-microbe interaction-related immune pathways alter the regenerative property of skin SCs. Last, we touch on mechanisms by which known immunologic cellular and molecular signaling might boost the skin's regenerative property. Overall, this review will provide insights into how therapeutically modulating immune signaling could enhance postnatal tissue regeneration.