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Keratinocyte Apoptosis in Epidermal Remodeling and Clearance of Psoriasis Induced by UV Radiation

Lookup NU author(s): Dr Sophie Weatherhead, Professor Peter Farr, Dr David Jamieson, Dr Jennifer Hallinan, Dr James Lloyd, Professor Anil Wipat, Professor Nick Reynolds

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Abstract

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.


Publication metadata

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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