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| Item Type: | Article |
|---|---|
| Title: | IL-10 controls ultraviolet-induced carcinogenesis in mice |
| Creators Name: | Loser, K., Apelt, J., Voskort, M., Mohaupt, M., Balkow, S., Schwarz, T., 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 |
| ISSN: | 0022-1767 |
| Publisher: | American Association of Immunologists |
| Volume: | 179 |
| Number: | 1 |
| 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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