Transient skin stretching stimulates immune surveillance and promotes vaccine delivery via hair follicles

Upon tissue injury, skin mechano-sensing promotes immune defense and return to homeostasis. However, the impact of acute skin stretching, such as skin rubbing, is poorly understood. Using a model of transient skin stretching, we show that a single instance of skin tension modification induces collagen fiber re-orientation, mechano-transduction in stromal cells, inflammatory mediator production, and immune cell recruitment to the skin. At the same time, skin stretching increases skin permeability without tissue damage via the opening of hair follicles. Furthermore, stretch-induced skin changes lead to the activation and migration of dermal dendritic cells through exposure to skin microbiota-derived compounds. Finally, we harness acute skin stretching to enable needle-free vaccine delivery, promoting antigen accumulation in the lymph nodes and producing a superior response compared to intramuscular injection. Our results shed light on the role of mechanical stimuli in fine-tuning skin immune surveillance and have important implications for drug delivery and mechanobiology.