Epigenetic immune memory in chronic inflammatory dermatoses: tissue-resident programming, barrier dysfunction and disease recurrence

Abstract

Chronic inflammatory dermatoses, including psoriasis, atopic dermatitis, vitiligo and hidradenitis suppurativa, are characterized by recurrent inflammation that often re-emerges at previously affected sites, despite apparent clinical resolution. Increasing evidence suggests that these disorders are sustained by persistent inflammatory memory involving tissue-­resident immune cells, keratinocyte reprogramming and durable epigenetic remodelling. Tissue-resident memory T cells can persist in clinically resolved skin and rapidly produce pathogenic cytokines upon reactivation, while keratinocytes may acquire transcriptional states that reinforce barrier dysfunction and inflammatory responsiveness. Cytokine-driven changes in histone acetylation, enhancer accessibility, DNA methylation and chromatin organization may leave cells in a primed inflammatory state, in which pathogenic pathways remain more accessible and easier to reactive after clinical healing. Environmental and metabolic factors, including microbial dysbiosis, obesity, smoking and chronic stress, may further reinforce these programmes by altering immune signalling and chromatin accessibility. Together, these findings support a model in which chronic dermatoses represent persistently altered tissue states rather than isolated inflammatory episodes. Recognition of inflammatory memory as a driver of disease recurrence has important translational implications, suggesting that future therapies may shift from transient inflammatory suppression towards targeted reprogramming of pathogenic immune memory.