Our second IMMOX conference will provide a forum for researchers, biologists and computational modellers interested in understanding the molecular pathogenesis of barrier disorders. Intestinal, lung and skin epithelia for barriers that are essential for life, supporting essential physiological functions while preventing microbial disregulation of the underlying mucosa. In this year’s programme, we gather experts in systems medicine to discuss mechanisms of host microbial symbiosis at the barrier; how germline and somatic genetic changes influence barrier health; how the adaptive immune system interprets surface barrier cues and how the epithelial niche contributes to barrier regeneration. We explore how computational and technical advances are transforming our understanding of barrier molecular pathology and informing novel design advances geared to harness immunity to combat disease.