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Lookup NU author(s): Dr Sophie Weatherhead, Professor Peter Farr, Dr David Jamieson, Dr Jennifer Hallinan, Dr James LloydORCiD, Professor Anil Wipat, Professor Nick ReynoldsORCiD
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Psoriasis is a common chronic skin disorder, but the mechanisms involved in the resolution and clearance of plaques remain poorly defined. We investigated the mechanism of action of UVB, which is highly effective in clearing psoriasis and inducing remission, and tested the hypothesis that apoptosis is a key mechanism. To distinguish bystander effects, equal erythemal doses of two UVB wavelengths were compared following in vivo irradiation of psoriatic plaques; one is clinically effective (311 nm) and one has no therapeutic effect on psoriasis (290 nm). Only 311 nm UVB induced significant apoptosis in lesional epidermis, and most apoptotic cells were keratinocytes. To determine clinical relevance, we created a computational model of psoriatic epidermis. Modeling predicted apoptosis would occur in both stem and transit-amplifying cells to account for plaque clearance; this was confirmed and quantified experimentally. The median rate of keratinocyte apoptosis from onset to cell death was 20 minutes. These data were fed back into the model and demonstrated that the observed level of keratinocyte apoptosis was sufficient to explain UVB-induced plaque resolution. Our human studies combined with a systems biology approach demonstrate that keratinocyte apoptosis is a key mechanism in psoriatic plaques clearance, providing the basis for future molecular investigation and therapeutic development.
Author(s): Weatherhead SC, Farr PM, Jamieson D, Hallinan JS, Lloyd JL, Wipat A, Reynolds NJ
Publication type: Article
Publication status: Published
Journal: Journal of Investigative Dermatology
Year: 2011
Volume: 131
Issue: 9
Pages: 1916-1926
Print publication date: 26/05/2011
ISSN (print): 0022-202X
ISSN (electronic): 1523-1747
Publisher: Nature Publishing Group
URL: http://dx.doi.org/10.1038/jid.2011.134
DOI: 10.1038/jid.2011.134
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