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Evidence that Singlet Oxygen-induced Human T Helper Cell Apoptosis Is the Basic Mechanism of Ultraviolet-A Radiation Phototherapy
Authors:Akimichi Morita   Thomas Werfel   Helger Stege   Constanze Ahrens   Karin Karmann   Markus Grewe   Susanne Grether-Beck   Thomas Ruzicka   Alexander Kapp   Lars-Oliver Klotz   Helmut Sies     Jean Krutmann
Affiliation:From *Clinical and Experimental Photodermatology, Department of Dermatology, Heinrich-Heine-University of Düsseldorf, D-40225 Düsseldorf; Department of Dermatology, Hannover Medical School, D-30625 Hannover; and §Institute of Physiological Chemistry I, Heinrich-Heine-University, D-40225 Düsseldorf, Germany
Abstract:Ultraviolet A (UVA) irradiation is effectively used to treat patients with atopic dermatitis and other T cell mediated, inflammatory skin diseases. In the present study, successful phototherapy of atopic dermatitis was found to result from UVA radiation-induced apoptosis in skin-infiltrating T helper cells, leading to T cell depletion from eczematous skin. In vitro, UVA radiation-induced human T helper cell apoptosis was mediated through the FAS/FAS-ligand system, which was activated in irradiated T cells as a consequence of singlet oxygen generation. These studies demonstrate that singlet oxygen is a potent trigger for the induction of human T cell apoptosis. They also identify singlet oxygen generation as a fundamental mechanism of action operative in phototherapy.
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