IL-10 controls ultraviolet-induced carcinogenesis in mice
IL-10 controls ultraviolet-induced carcinogenesis in mice
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DOI：
10.4049/jimmunol.179.1.365
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发表时间：
2007-07-01
影响因子：
4.4
通讯作者：
Beissert, Stefan
中科院分区：
文献类型：
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作者：
Loser, Karin;Apelt, Jenny;Beissert, Stefan
紫外线辐射诱导的免疫抑制通过抑制保护性免疫反应而显著促进紫外线诱导的皮肤癌的发展。IL-10已被证明是UV诱导的免疫抑制的关键介质。为了研究IL-10在光致癌过程中的作用，IL-10（+/+）、IL-10（+/-）和IL-10（-/-）小鼠组用UV长期照射。IL-10（+/+）和IL-10（+/-）小鼠发生皮肤癌的程度相似，而IL-10（-/-）小鼠则可免受紫外线诱导的皮肤恶性肿瘤的影响。因为UV能够诱导调节性T细胞，其在抑制保护性免疫中起作用，所以分析了UV诱导的调节性T细胞功能。来自经UV照射的IL-10（-/-）小鼠的脾调节性T细胞在转移至初始受体后不能赋予免疫抑制。来自IL-10（-/-）小鼠的UV诱导的CD 4（+）CD 25（+）T细胞在与常规的CD 4（+）CD 25（-）T细胞共培养时显示抑制功能受损。IL-10（-/-）小鼠的CD 4（+）CD 25（-）T细胞产生的IFN-γ数量增加，在IL-10（-/-）小鼠的UV诱导肿瘤中可检测到CD 4（+）TIM-3（+）T细胞数量增加，表明Th 1驱动的免疫力较强。用来自UV照射的IL-10（-/-）小鼠的CD 8（+）T细胞处理的小鼠明显更快地拒绝UV肿瘤攻击，并且在IL-10（-/-）动物中注射的UV肿瘤内检测到颗粒酶A（+）细胞的增加，表明显著的抗肿瘤CTL应答。总之，这些发现表明IL-10在光致癌过程中参与抗肿瘤免疫。此外，这些结果指出了Th 1应答和UV诱导的调节性T细胞功能在保护免受UV诱导的肿瘤发展中的关键作用。
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-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.