Nature

The skin barrier is the body’s first line of defence against environmental assaults, and is maintained by epithelial stem  cells (EpSCs). Despite the vulnerability of EpSCs to inflammatory pressures, neither the primary response to inflammation  nor its enduring consequences are well understood. Here we report a prolonged memory to acute inflammation that  enables mouse EpSCs to hasten barrier restoration after subsequent tissue damage. This functional adaptation does not  require skin-resident macrophages or T cells. Instead, EpSCs maintain chromosomal accessibility at key stress response  genes that are activated by the primary stimulus. Upon a secondary challenge, genes governed by these domains are  transcribed rapidly. Fuelling this memory is Aim2, which encodes an activator of the inflammasome. The absence of AIM2  or its downstream effectors, caspase-1 and interleukin-1β, erases the ability of EpSCs to recollect inflammation. Although  EpSCs benefit from inflammatory tuning by heightening their responsiveness to subsequent stressors, this enhanced  sensitivity probably increases their susceptibility to autoimmune and hyperproliferative disorders, including cancer.