Born to Scratch: Towards Cutaneous Microtrauma in Newborns as a Driver of Immune Imprinting

Neonatal self-scratching, often considered a harmless mechanical reflex, may play a more influential role in shaping early immune system development than previously recognized. We hypothesize that superficial cutaneous microtrauma caused by healthy newborn scratching may contribute to immune imprinting through localized inflammatory responses and antigen exposure. We developed a time-resolved stochastic model to simulate antigen encounter, microbial presence and antigen capture dynamics in the context of superficial skin injury, to evaluate the likelihood of immune activation resulting from epidermal disruption. By varying parameters such as injury depth, microbial density and antigen presentation probability, we quantified their respective impacts on cumulative immune priming outcomes across simulated conditions. Simulations show that even shallow skin injuries, when combined with microbial ingress and effective antigen presentation, can exceed activation thresholds necessary for initiating early immune priming. Results indicate that a cascade of innate immune events, including keratinocyte activation, cytokine release and engagement of antigen-presenting cells, could be initiated by the minor skin abrasions commonly observed during neonatal scratching. This model supports a plausible mechanism through which seemingly minor mechanical injuries may contribute to early immune training. By treating the skin not merely as a passive barrier but as an active immunological interface, our approach recontextualizes common neonatal behaviours within a meaningful immunological framework. If validated, our hypothesis suggests that controlled microtrauma or targeted skin exposure in newborns could serve as a strategy to support immune development in a safe manner. Still, population-level modeling may allow translation from individual simulations to public health insights.