Abstract
The skin transforms environmental stimuli into biological signals, allowing the body to adapt appropriately to external stress. In particular, skin mechano-sensing promotes immune defence in response to tissue injury. However, the impact of more subtle stimuli, such as transient mechanical stimulation, on immune surveillance is unknown. By perturbing skin tension to the extent experienced during skin massage, we find that transient skin stretching modifies collagen fiber orientation and induces mechano-transduction in stromal cells, producing inflammatory mediators and recruiting innate immune cells. In parallel, skin stretching increases tissue permeability via reversible opening of appendages that promotes transdermal macromolecule penetration without disrupting the stratum corneum or producing damage-associated alarmins. This phenomenon stimulates dermal dendritic cell activation and migration through exposure to skin microbiota-derived compounds. We demonstrate that the effects of transient stretching enable needle-free vaccine delivery into the skin. Stretching-mediated delivery promotes antigen accumulation in the lymph nodes and produces a superior response compared to a dose-matched intra-muscular injection. Our results shed light on the role of mechanical stimuli in fine-tuning skin immune surveillance and have important implications for drug delivery, environmental toxicology and mechanobiology.