Apoptosis of keratinocytes is a key mechanism in UVB-induced clearance of psoriasis

Sophie C. Weatherhead, Peter M. Farr, Daniel Swan, David Jamieson, Jennifer Hallinan, James J. Lloyd, Anil Wipat, Nicholas Reynolds

Research output: Contribution to journalMeeting abstract

Abstract

The mechanisms underlying UVB-induced clearance of psoriasis are incompletely understood. We compared the cellular and molecular effects of a clinically effective wavelength of UVB (311nm) with a clinically ineffective wavelength (290nm) in vivo and in vitro to distinguish bystander effects and utilised a systems biology approach to understand functional significance. 84 adult psoriatic patients were recruited. Biopsies were taken from lesional (plaque) skin before and 4-48h after irradiation with equi-erythemogenic doses of 311 and/or 290nm UVB (0.75-3.0 MED). A significant increase in the numbers of apoptotic epidermal cells (active-caspase-3+ cells) was seen after a single irradiation with 2-3 MEDs 311 nm UVB compared to 2-3 MEDs 290 nm UVB or untreated psoriasis (median 12/1000, 0/1000 and 0/1000 epidermal cells respectively; p<0.001). Routine clinical doses of 311nm also induced apoptosis. Immunochemistry and electron microscopy showed that the vast majority of apoptotic cells were keratinocytes. Live cell imaging of irradiated cultured keratinocytes and mathematical modelling showed that the rate of keratinocyte apoptosis observed in vivo was sufficient to account for clearance of psoriasis. Gene array analysis was used to examine differential gene regulation at these early time-points, prior to clinical response. Apoptosis and control of cell cycle pathways were affected by 311nm but not 290nm UVB. CDKN1A (WAF1/p21) showed the greatest fold change (27 fold up-regulation) following irradiation with 311nm UVB but not 290nm. Together these data provide evidence that epidermal keratinocyte apoptosis is a key mechanism in psoriasis resolution and identifies keratinocyte apoptosis as a potential target for future drug development.
Original languageEnglish
Article number392
Pages (from-to)S66-S66
Number of pages1
JournalJournal of Investigative Dermatology
Volume131
Issue numberSupplement 2
DOIs
Publication statusPublished - Sep 2011
Externally publishedYes
Event41st Annual Meeting of the European-Society-for-Dermatological-Research - Barcelona, Spain
Duration: 7 Sep 201110 Sep 2011

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