Cellular Immunology Group, Department of Infectious Diseases and Immunology, Sydney Medical School, University of Sydney, New South Wales, Australia.
Am J Pathol. 2011 Jul;179(1):211-22. doi: 10.1016/j.ajpath.2011.03.010. Epub 2011 May 13.
The cellular and molecular mechanisms by which UV radiation modulates inflammation and immunity while simultaneously maintaining skin homeostasis is complex and not completely understood. Similar to the effects of UV, IL-33 has potent immune-modulating properties that are mediated by the downstream induction of cytokines and chemokines. We have discovered that exposure of mice in vivo or human skin samples ex vivo to inflammatory doses of UVB induced IL-33 expression within the epidermal and dermal skin layers. Using a combination of murine cell lines and primary human cells, we demonstrate that both UV and the oxidized lipid platelet activating factor induce IL-33 expression in keratinocytes and dermal fibroblasts. Highlighting the significance of these results, we found that administering IL-33 to mice in vivo suppressed the induction of Th1-mediated contact hypersensitivity responses. This may have consequences for skin cancer growth because UV-induced squamous cell carcinomas that evade immunological destruction were found to express significantly higher levels of IL-33. Finally, we demonstrate that dermal mast cells and skin-infiltrating neutrophils closely associate with UV-induced IL-33-expressing fibroblasts. Our results therefore identify and support a role for IL-33 as an important early danger signal produced in response to inflammation-inducing UV radiation.
UV 辐射调节炎症和免疫同时维持皮肤稳态的细胞和分子机制很复杂，目前尚未完全阐明。与 UV 的作用相似，IL-33 具有强大的免疫调节特性，这是通过下游细胞因子和趋化因子的诱导介导的。我们发现，体内暴露于小鼠或离体的人类皮肤样本于炎性剂量的 UVB 会诱导表皮和真皮皮肤层中的 IL-33 表达。我们使用鼠类细胞系和原代人细胞的组合，证明了 UV 和氧化脂质血小板激活因子均可诱导角质形成细胞和真皮成纤维细胞中 IL-33 的表达。突出这些结果的重要性，我们发现，体内给予 IL-33 可抑制 Th1 介导的接触性过敏反应的诱导。这可能对皮肤癌的生长产生影响，因为逃避免疫破坏的 UV 诱导的鳞状细胞癌被发现表达显著更高水平的 IL-33。最后，我们证明真皮肥大细胞和皮肤浸润的中性粒细胞与 UV 诱导的表达 IL-33 的成纤维细胞密切相关。因此，我们的研究结果确定并支持了 IL-33 作为一种重要的早期危险信号，在炎症诱导的 UV 辐射下产生。
