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

      Highlights

      • First study on the effect of NB-UVB in perilesional psoriasis using RNA-seq.
      • NB-UVB suppressed NF-kB and upregulated sirtuin pathway.
      • NB-UVB decreased the function of IL-17 pathway, and toll-like receptor pathway.
      • NB-UVB treatment was associated with increased expression of SKP1.
      • NB-UVB treatment decreased expression of NFKBIZ, SERPINB4, ATG13, and CTSS.

      Abstract

      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 associated 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 potential treatment targets.

      Keywords

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