IL-10 Controls Ultraviolet-Induced Carcinogenesis in Mice

• Published in: Journal of Immunology 2007-07, Vol.179 (1), p.365-371
• Main Authors: Loser, Karin, Apelt, Jenny, Voskort, Maik, Mohaupt, Mariette, Balkow, Sandra, Schwarz, Thomas, Grabbe, Stephan, Beissert, Stefan
• Format: Article
• Language: English
• Subjects: Animals; Cytokines - biosynthesis; Immune Tolerance - genetics; Immune Tolerance - radiation effects; Interleukin-10 - deficiency; Interleukin-10 - genetics; Interleukin-10 - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Nude; Neoplasms, Radiation-Induced - genetics; Neoplasms, Radiation-Induced - immunology; Neoplasms, Radiation-Induced - pathology; Neoplasms, Radiation-Induced - prevention & control; Skin Neoplasms - genetics; Skin Neoplasms - immunology; Skin Neoplasms - pathology; Skin Neoplasms - prevention & control; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - pathology; T-Lymphocytes, Regulatory - radiation effects; Ultraviolet Rays
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.179.1.365

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.