Quantitative analysis of JAK/STAT signaling pathway in patients of inflammatory skin disorders.

Abstract

Inflammatory skin diseases (ISDs), are characterized by dysregulated activation of innate and adaptive immune systems, with inflammatory cytokines playing a crucial role in their pathogenesis. This study aimed to investigate the involvement of Janus kinase/signal transduction and activator of transcription (JAK/STAT) signaling pathway in the pathogenesis of ISDs. The study analyzed a total of 117 skin biopsies, comprising 31 from pyoderma gangrenosum (PG), 25 from hidradenitis suppurativa (HS), 35 from psoriasis patients, and 26 from control subjects. To assess the expression levels of JAK/STAT pathway components, immunohistochemical staining was performed on both the dermal and epidermal layers of the skin. The Histo score (H score) was utilized as the immunoexpression score to evaluate the staining intensity. The results indicated that all components of the JAK/STAT signaling pathway, except JAK2 and STAT6 in PG, JAK1, STAT4, and STAT6 in HS, and JAK1 in psoriasis, were overexpressed in the dermal skin compared to the control group (p < 0.05). Psoriatic skin had higher expression of STAT6 than both PG and HS and higher expression of JAK2 than PG (p < 0.05). Additionally, HS biopsies had higher expression of JAK2 and STAT6 compared to PG (p < 0.05). JAK1 expression was higher in PG than in HS, psoriasis, and the control group (mean H score was 265.8, 184.8, 191.4, and 113.1, p < 0.05, respectively). This study provides new insights into the potential contribution of the JAK/STAT pathway to the pathogenesis of ISDs. The findings suggest that targeting this pathway could be a promising therapeutic strategy for treating these disorders.