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* Department of Dermatology and Interdisciplinary Center of Clinical Research, Interdisziplinäres Zentrum für Klinische Forschung, University of Münster, Münster, Germany;
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany;
Department of Dermatology, University of Kiel, Kiel, Germany; and
Department of Dermatology, University of Mainz, Mainz, Germany
UV radiation-induced immunosuppression contributes significantly to the development of UV-induced skin cancer by inhibiting protective immune responses. IL-10 has been shown to be a key mediator of UV-induced immunosuppression. To investigate the role of IL-10 during photocarcinogenesis, groups of IL-10+/+, IL-10+/–, and IL-10–/– mice were chronically irradiated with UV. IL-10+/+ and IL-10+/– mice developed skin cancer to similar extents, whereas IL-10–/– mice were protected against the induction of skin malignancies by UV. Because UV is able to induce regulatory T cells, which play a role in the suppression of protective immunity, UV-induced regulatory T cell function was analyzed. Splenic regulatory T cells from UV-irradiated IL-10–/– mice were unable to confer immunosuppression upon transfer into naive recipients. UV-induced CD4+CD25+ T cells from IL-10–/– mice showed impaired suppressor function when cocultured with conventional CD4+CD25– T cells. CD4+CD25– T cells from IL-10–/– mice produced increased amounts of IFN-
and enhanced numbers of CD4+TIM-3+ T cells were detectable within UV-induced tumors in IL-10–/– mice, suggesting strong Th1-drived immunity. Mice treated with CD8+ T cells from UV-irradiated IL-10–/– mice rejected a UV tumor challenge significantly faster, and augmented numbers of granzyme A+ cells were detected within injected UV tumors in IL-10–/– animals, suggesting marked antitumoral CTL responses. Together, these findings indicate that IL-10 is critically involved in antitumoral immunity during photocarcinogenesis. Moreover, these results point out the crucial role of Th1 responses and UV-induced regulatory T cell function in the protection against UV-induced tumor development.
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1 This work was supported by German Research Association (Deutsche Forschungsgemeinschaft) Grants BE 1580/7-1 (to S.B.) and SCHW 1177/1-1 (to T.S.), Interdisciplinary Center of Clinical Research (Interdisziplinäres Zentrum für Klinische Forschung) Grant Lo2/017/07 (to K.L. and S.B.), and the fund "Innovative Medical Research" of the University of Münster Medical School Grant Lo11/06 03 (to K.L. and S.B.).
2 K.L. and J.A. share equal authorship.
3 Address correspondence and reprint requests to Dr. Stefan Beissert, Department of Dermatology, University of Münster, Von-Esmarch-Strasse 58, Münster, Germany. E-mail address: beisser{at}uni-muenster.de
4 Abbreviations used in this paper: CHS, contact hypersensitivity; DNFB, 2,4-dinitrofluorobenzene; GrzA, granzyme A.
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