Transcriptome profiling in psoriasis: NB-UVB treatment-associated transcriptional changes and modulation of autoinflammation in perilesional skin in early-phase disease

Background: Psoriasis is a chronic inflammatory skin condition. It is widely treated with phototherapy using narrowband ultraviolet B (NB-UVB). The therapeutic mechanisms of NB-UVB, however, remain unclear, particularly in the early phases of the disease. Objective: To investigate the mechanisms underlying the effects of NB-UVB on psoriasis in a model of perilesional psoriasis.Methods: Psoriatic patients that received NB-UVB treatment and were evaluated with the psoriasis area and severity index were included in the study. Skin biopsies obtained before and after treatment were subjected to RNA sequencing (RNA-seq) and Ingenuity Pathway Analyses for genome-wide transcriptome profiling to gain further insights into the signaling pathways underlying the improvement of psoriasis with therapeutic intervention.Results: Our findings revealed that NB-UVB treatment may exert its effects by suppressing nuclear factor kappa B, which leads to upregulation of the sirtuin signaling pathway, as well as by decreasing the function of major upstream regulators associated with proinflammatory and inflammatory cytokines, which blocks the expression of downstream toll-like receptors. Psoriasis improvement after NB-UVB treatment was as-sociated with decreased expression of NFKBIZ, SERPINB4, ATG13, and CTSS and increased expression of SKP1 gene. Our results also highlighted the expression of proposed genes associated with the modulation of autoinflammation.Conclusions: To the best of our knowledge, this is the first study to apply advanced molecular techniques to explore the effects of phototherapy on psoriasis in the early-phase, providing new insights into the disease pathogenesis and novel genetic information for the development of new therapeutic modalities and po-tential treatment targets.(c) 2022 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Automated summary

Through RNA sequencing and pathway analysis, the study found that NB-UVB treatment may improve psoriasis by suppressing NF-κB, enhancing sirtuin signaling pathway, and decreasing the function of key upstream regulators associated with proinflammatory cytokines. The study also highlighted the gene expression changes associated with the modulation of autoinflammation after NB-UVB treatment.