IL-10 controls ultraviolet-induced carcinogenesis in mice.
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.
Loser
Karin
K
Department of Dermatology and Interdisciplinary Center of Clinical Research, Interdisziplinäres Zentrum für Klinische Forschung, University of Münster, Von-Esmarch-Strasse 58, Münster, Germany.
Apelt
Jenny
J
Voskort
Maik
M
Mohaupt
Mariette
M
Balkow
Sandra
S
Schwarz
Thomas
T
Grabbe
Stephan
S
Beissert
Stefan
S
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D007108:Immune Tolerance / Q000235:genetics / Q000528:radiation effects; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D009381:Neoplasms, Radiation-Induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology / Q000528:radiation effects; D014466:Ultraviolet Rays
D016207:Cytokines; D016753:Interleukin-10