Chromatin Accessibility Profiling of Keratinocytes from Clinically Healed Psoriatic Skin Reveals Epigenetic...

Psoriasis is a chronic inflammatory skin disease with recurrence that often reappears at previously affected sites, suggesting an epigenetic imprint in healed skin. However, the chromatin landscape of clinically healed psoriatic keratinocytes remains uncharacterized. We performed Assay for Transposase-Accessible Chromatin using sequencing on epidermal keratinocytes isolated from psoriasis-affected, clinically healed, and control skin samples. Compared with those of healthy skin, psoriasis-affected keratinocytes exhibited widespread alterations in chromatin accessibility. Although most of these disease-associated changes resolved after clinical remission, 152 peaks remained differentially accessible, particularly at NF-κB-associated immune-regulatory loci, including S100A7/A8/A9 and IL36G. Despite this residual chromatin accessibility, immunohistochemistry revealed a lack of detectable protein expression in healed keratinocytes, reflecting a transcriptionally poised but translationally inactive state. Pathway analysis revealed 2 recovery patterns: low-recovery peaks enriched for inflammatory pathways and high-recovery peaks linked to cytoskeletal remodeling and metabolism. These findings demonstrate that postremission keratinocytes retain a chromatin signature distinct from both affected and healthy skin. A limitation of this study is the absence of never-involved skin in assessing whether the chromatin changes identified are specific to previously affected skin. Nevertheless, this study provides insight into the molecular basis of disease memory that may underlie the skin's susceptibility to relapse in psoriasis.