Hart P H, Grimbaldeston M A, Jaksic A, Tan J E, Swift G J, Hosszu E K, Halliday G M, Finlay-Jones J J
Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University, Adelaide, Australia.
J Invest Dermatol. 2000 Mar;114(3):508-13. doi: 10.1046/j.1523-1747.2000.00909.x.
Ultraviolet B radiation is immunosuppressive by multiple mechanisms. In interleukin-4-/- mice, ultraviolet B radiation was not able to suppress delayed-type hypersensitivity or contact hypersensitivity responses when the sensitizing antigen was applied to nonirradiated sites. In contrast, ultraviolet B significantly suppressed contact hypersensitivity responses to haptens applied to irradiated sites in interleukin-4-/- mice. In mast cell depleted Wf/Wf mice, ultraviolet B radiation also significantly suppressed contact hypersensitivity responses to sensitizing antigens applied to irradiated but not to unirradiated sites. In both interleukin-4-/- mice and Wf/Wf mice, the mast cell product, histamine, was immunosuppressive implicating mast cells as the dysfunctional cell in interleukin-4-/- mice. The prevalence of dermal mast cells was similar in wild-type and interleukin-4-/- mice. Dermal mast cells of interleukin-4-/- mice, however, express very low levels of c-kit and did not significantly degranulate in response to ultraviolet B. Ultraviolet radiation induced significant and similar levels of serum interleukin-10 in wild-type and interleukin-4-/- mice. We conclude that interleukin-4 indirectly affects ultraviolet B suppression of contact hypersensitivity and delayed-type hypersensitivity responses to sensitizing antigens applied at sites other than those irradiated by providing a critical differentiative signal for dermal mast cells. This study further emphasizes the central role of mast cells in the initial processes by which ultraviolet B radiation is immunomodulatory for immune responses to sensitizing antigens applied to nonirradiated sites.
紫外线B辐射通过多种机制产生免疫抑制作用。在白细胞介素-4基因敲除小鼠中，当致敏抗原应用于未照射部位时，紫外线B辐射无法抑制迟发型超敏反应或接触性超敏反应。相比之下，紫外线B能显著抑制白细胞介素-4基因敲除小鼠中应用于照射部位的半抗原引起的接触性超敏反应。在肥大细胞缺失的Wf/Wf小鼠中，紫外线B辐射也能显著抑制应用于照射部位而非未照射部位的致敏抗原引起的接触性超敏反应。在白细胞介素-4基因敲除小鼠和Wf/Wf小鼠中，肥大细胞产物组胺都具有免疫抑制作用，这表明肥大细胞是白细胞介素-4基因敲除小鼠中功能失调的细胞。野生型小鼠和白细胞介素-4基因敲除小鼠的皮肤肥大细胞患病率相似。然而，白细胞介素-4基因敲除小鼠的皮肤肥大细胞c-kit表达水平非常低，且对紫外线B照射无明显脱颗粒反应。紫外线辐射在野生型小鼠和白细胞介素-4基因敲除小鼠中诱导产生的血清白细胞介素-10水平显著且相似。我们得出结论，白细胞介素-4通过为皮肤肥大细胞提供关键的分化信号，间接影响紫外线B对应用于未照射部位的致敏抗原引起的接触性超敏反应和迟发型超敏反应的抑制作用。这项研究进一步强调了肥大细胞在紫外线B辐射对应用于未照射部位的致敏抗原免疫反应进行免疫调节的初始过程中的核心作用。
