Psoriasis is a chronic inflammatory, immune mediated skin and systemic disease with debilitating and life limiting effects. Currently patients are treated on a trial and error basis highlighting the need for predictive biomarkers.  Phototherapy is an effective therapy and may induce remission. Previous work showed that 311nm UVB (effective in clearing psoriasis) but not by 290nm UVB (ineffective in clearing psoriasis) induced apoptosis in lesional psoriatic skin.  The aim of this study was to investigate the molecular mechanisms regulating psoriasis plaque resolution in response to UVB and to identify potential biomarkers.

Bioinformatic analysis was performed on microarray data derived from skin biopsies (n=48) obtained 4h and 18h after irradiation of psoriatic skin with 311nm or 290nm UVB. Differentially expressed genes (DEGs) associated with 311nm but not 290nm were analysed for their upstream regulators (IPA). Validation, localisation patterns and quantification of biomarkers was determined using immunofluorescence and Volocity.

Eliminating genes induced by 290nm resulted in 755 and 795 DEGs regulated by 311nm at 4h and 18h respectively. Upstream analysis showed that the commonest pathways regulated by 311nm (but not 290nm) in psoriasis skin were apoptosis and necrosis which appeared to be occurring in a variety of cell types.  In terms of canonical pathways, we found differential modulation of acute phase signalling (including IL-1 and p38), p53, IL17a and atherosclerosis signalling by 311nm compared to 290nm UVB.  FOSL1, JUNB, GDF15 and p21, proteins implicated in apoptosis, were differentially induced by 311nm compared to 290nm.

Our microarray analysis confirmed apoptosis and necrosis as key cellular processes differentially induced by 311nm UVB compared to 290 but also identified pathways relevant to psoriasis and its associated co-morbidities. Together with our earlier work, these data support a key role for apoptosis and necrosis in addition to psoriasis cytokine networks in plaque clearance.

Role of apoptosis and key canonical pathways in psoriasis plaque clearance in response to UVB phototherapy