Toke Touborg

Atopic dermatitis is a common inflammatory skin disease affecting up to 10% of adults. Whether atopic dermatitis exhibits a strong systemic inflammatory signature remains debated. We characterized peripheral whole-blood alterations in adults with moderate-to-severe atopic dermatitis undergoing treatment with dupilumab or baricitinib therapy. Blood samples were collected at weeks 0, 4, and 16. Whole-blood proteins were measured using Olink, transcriptomic profiling was performed by RNA sequencing, and torque teno virus plasma levels were quantified by qPCR. During targeted atopic dermatitis therapy with dupilumab or baricitinib, clustering of samples based on gene expression levels showed no separation by time or treatment, with only a limited number of differentially expressed genes. Proteomic changes were similarly modest; however, treatment was consistently associated with decreased CCL17/TARC levels. Teno torque virus plasma load remained stable throughout therapy, indicating preserved immunocompetence. These findings suggest that the dominant inflammatory processes in atopic dermatitis may be largely tissue-restricted, supporting the use of peripheral biomarkers for pragmatic monitoring rather than mechanistic discovery.

IκBζ (NFKBIZ) has been implicated as a key co-transcription factor in psoriasis pathogenesis. While its role in keratinocytes is well established, the involvement in dermal fibroblasts, another critical skin cell type, remains underexplored. This study characterizes cytokine-induced NFKBIZ regulation in human dermal fibroblasts in vitro and integrates spatial transcriptomics to determine NFKBIZ expression patterns in psoriatic skin biopsies. Primary dermal fibroblasts were stimulated with IL-17A, IL-17F, and TNF. Signaling pathways and gene regulation were examined using chemical inhibitors, siRNA knockdown, qPCR, and Western blotting. Additionally, spatial transcriptomics (CosMx™) assessed NFKBIZ expression in paired lesional and non-lesional psoriatic skin biopsies. Results showed significant upregulation of IκBζ expression in dermal fibroblasts following stimulation with both IL-17A and IL-17F. The NF-κB signaling pathway was identified as the primary regulator of NFKBIZ induction. NFKBIZ knockdown significantly reduced cytokine-induced expression of inflammatory mediators (CXCL8, CCL20, CCL2), confirming its regulatory role. Spatial transcriptomics further confirmed NFKBIZ expression in dermal fibroblasts in vivo, particularly in lesional psoriatic skin. This study establishes IκBζ as a critical modulator of inflammatory responses in dermal fibroblasts, expanding its recognized role beyond keratinocytes and immune cells, and highlights IκBζ inhibition as a potential therapeutic strategy.