Cutaneous adipose tissue carries a strong inflammatory signature in patients with psoriasis.

This study provides a comprehensive evaluation of the cutaneous adipose tissue (CAT) transcriptome in patients with psoriasis and investigates the effects of IL-17 blockade on CAT inflammation through a randomized placebo-controlled trial using secukinumab (ObePso-S study, ClinicalTrials.gov NCT03055494). RNA sequencing analysis of CAT biopsies from 82 patients with psoriasis revealed 2132 differentially expressed transcripts compared with healthy controls. Notably, significant gene dysregulation was observed in both lesional skin (LS)-CAT and non-lesional (NL)-CAT, including activation of IL-17-driven pathways, antimicrobial peptide-related, and neutrophil degranulation signatures. Stratification by obesity demonstrated that obese psoriatic CAT exhibited a more than 2-fold higher number of differentially expressed genes than non-obese counterparts, suggesting a synergistic interaction between psoriasis and obesity in driving CAT inflammation. Treatment with secukinumab markedly improved inflammatory signatures in psoriatic CAT, with greater improvements observed in obese patients. These findings reveal a pronounced and partially IL-17-dependent inflammatory phenotype in psoriatic CAT, challenge the conventional concept of psoriasis as a solely superficial skin disease, and highlight CAT as an important contributor to systemic inflammation in psoriasis.