Epigenetic reprogramming in autoimmune and immune-mediated skin disease
TL;DR
It is suggested that achieving durable therapeutic remission may require reprogramming pathogenic chromatin states rather than solely suppressing inflammatory pathways.
Abstract
Background Autoimmune skin diseases exhibit chronicity and site-specific relapse that are not fully explained by genetic susceptibility or cytokine signaling alone. Emerging evidence suggests that epigenetic reprogramming of skin-resident immune cells contributes to disease persistence and recurrence. Methods We conducted a structured narrative review of the human literature by searching PubMed for studies published from database inception through March 1, 2026. The literature search was performed between February 1 and March 1, 2026 and focused on epigenetic mechanisms across major autoimmune dermatoses, including DNA methylation, histone modification, chromatin accessibility, non-coding RNA regulation, and emerging single-cell and spatial epigenomic technologies. Results Current evidence suggests stable chromatin remodeling in keratinocytes and immune cells, including tissue-resident memory T cells, that persists after clinical resolution and may facilitate rapid disease reactivation. Environmental exposures further reinforce these epigenetic programs, contributing to disease heterogeneity, chronicity, and site-specific relapse. Conclusion Collectively, these findings are consistent with a model in which autoimmune skin diseases are maintained by maladaptive epigenetic memory. Although causal inference remains limited by the relative scarcity of cell-type–resolved human epigenomic data and the predominance of cross-sectional studies, this framework suggests that achieving durable therapeutic remission may require reprogramming pathogenic chromatin states rather than solely suppressing inflammatory pathways.