How epithelial stem cells (EpSCs) that reside in the basal layer of the skin epithelium respond to inflammatory stimuli remains unclear. In Nature, Fuchs and colleagues show that skin EpSCs maintain prolonged memory of acute inflammation to induce rapid responses after subsequent tissue damage. Mice previously exposed to various inflammatory stimuli, such as imiquimod, abrasion wounding or Candida infection, heal wounds 2.5 times faster than do naive mice, even 180 days later. Inflammation-exposed skin shows proliferation rates similar to those of naive skin but accelerated re-epithelialization, a process still observed in mice deficient in the recombinase component RAG-2 or mice depleted of macrophages. At 30 days after exposure to imiquimod, EpSCs show greater chromatin accessibility in genes encoding molecules associated with inflammation, interleukin signaling, oxidative stress response and proliferation, relative to that of naive EpSCs. Those genes represent 50% of the genes upregulated 12 hours after secondary injury. Enhanced skin repair is lost in inflammation-exposed mice deficient in the AIM2 inflammasome or the IL-1 receptor IL-1R1, which indicates AIM2 and IL-1β are central regulators of EpSC memory.

Nature 550, 475–480 (2017)