Keratinocyte apoptosis in epidermal remodeling and clearance of psoriasis induced by UV radiation

Sophie C. Weatherhead, Peter M. Farr, David Jamieson, Jennifer S. Hallinan, James J. Lloyd, Anil Wipat, Nick J. Reynolds*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Citations (Scopus)
8 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)1916-1926
Number of pages11
JournalJournal of Investigative Dermatology
Volume131
Issue number9
DOIs
Publication statusPublished - Sep 2011
Externally publishedYes

Bibliographical note

Copyright the Society for Investigative Dermatology 2011. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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