Cutaneous adipose tissue has a strong inflammatory signature in psoriasis patients, and it is partly IL-17 dependent.

Background: Psoriasis is an inflammatory skin disease associated with systemic inflammation and comorbidities such as diabetes and cardiovascular disease. Although the association between psoriasis and obesity has been studied extensively, the role of cutaneous adipose tissue (CAT) in pathogenesis of psoriasis remains unclear. Objectives This study aimed to provide a comprehensive evaluation of the CAT transcriptome in psoriasis patients and investigate the effects of IL-17 pathway blockade on adipose tissue inflammation. Methods: In this randomized, double-blind, placebo-controlled phase 4 study (ObePso study), CAT biopsies were obtained from lesional (LS-CAT) and non-lesional skin (NL-CAT) of 82 psoriasis patients and 15 healthy controls. Patients were randomized to receive either secukinumab or placebo for 12 weeks. RNA sequencing and subsequent analyses were performed to identify differentially expressed genes and pathways. Results: Psoriatic CAT showed significant gene expression differences compared to controls, with 2132 differentially expressed transcripts identified. Both LS-CAT and NL-CAT exhibited activation of IL-17-induced, antimicrobial peptides-related, and neutrophil degranulation-related pathways. Obesity expanded differential gene expression in psoriasis by more than 100%, suggesting an additive or synergistic interaction between psoriasis and adiposity. Obese psoriasis patients showed activation of pathways related to collagen metabolism, cytokine storm signaling, and IL-17A signaling. Secukinumab treatment significantly improved inflammation in psoriatic CAT, with obese patients showing greater improvement than non-obese patients. Conclusions: This study provides the first comprehensive evaluation of the adipose tissue transcriptome in psoriasis patients. The findings reveal a strong inflammatory signature in psoriatic CAT, which is partly IL-17 dependent. The study also demonstrates that obesity amplifies the inflammatory response in psoriatic adipose tissue. IL-17 blockade with secukinumab significantly improved CAT inflammation, with enhanced benefits observed in obese individuals. These results highlight the potential role of adipose tissue in psoriasis pathogenesis and suggest that targeting adipose tissue inflammation may be a valuable therapeutic approach, particularly in obese psoriasis patients.