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IL-10 controls ultraviolet-induced carcinogenesis in mice

Item Type:Article
Title:IL-10 controls ultraviolet-induced carcinogenesis in mice
Creators Name:Loser, K. and Apelt, J. and Voskort, M. and Mohaupt, M. and Balkow, S. and Schwarz, T. and Grabbe, S. and Beissert, S.
Abstract: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-gamma and enhanced numbers of CD4+TIM-3+ T cells were detectable within UV-induced tumors in IL-10(-/-) mice, suggesting strong Th1-driven 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.
Keywords:Cytokines, Immune Tolerance, Inbred C57BL Mice, Interleukin-10, Knockout Mice, Nude Mice, Radiation-Induced Neoplasms, Regulatory T-Lymphocytes, Skin Neoplasms, Ultraviolet Rays, Animals, Mice
Source:Journal of Immunology
Publisher:American Association of Immunologists (U.S.A.)
Page Range:365-371
Date:1 July 2007
Official Publication:http://www.jimmunol.org/content/179/1/365.long
PubMed:View item in PubMed

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