Impact of dupilumab and upadacitinib treatment on epigenetic and transcriptomic alterations in skin-homing T cells of atopic dermatitis patients

Abstract

BackgroundBiologic therapies, such as the IL-4 receptor alpha blocker dupilumab, and Janus kinase (JAK) inhibitors like upadacitinib, have revolutionized the management of atopic dermatitis (AD). However, prolonged treatment is necessary to sustain disease remission. While both therapies are clinically effective, only dupilumab has demonstrated successful dose reduction, suggesting potential disease-modifying effects. This study investigates the immune-modulating potential of one year treatment with dupilumab or upadacitinib in AD by assessing epigenetic and transcriptomic changes in skin-homing T cells. MethodsUsing flow cytometry, CD4+CLA+ T cells were isolated from AD patients (n=12) at baseline and after 52 weeks of dupilumab (n=6) or upadacitinib (n=6) treatment. DNA methylome, RNA transcriptome and cytokines expression analyses were conducted using the EPIC array, RNA sequencing and flow cytometry, respectively. Non-atopic healthy controls (HC) (n=6) were included for comparison. ResultsWe identified 747 differentially methylated regions (DMRs) between HC and AD patients (p-value View larger version (28K): org.highwire.dtl.DTLVardef@2e442org.highwire.dtl.DTLVardef@1d7aa16org.highwire.dtl.DTLVardef@1df906corg.highwire.dtl.DTLVardef@82e1fd_HPS_FORMAT_FIGEXP M_FIG C_FIG