Kondo H, Ichikawa Y, Imokawa G
Biological Science Laboratory, Kao Corporation, Tochigi, Japan.
Eur J Immunol. 1998 Mar;28(3):769-79. doi: 10.1002/(SICI)1521-4141(199803)28:03<769::AID-IMMU769>3.0.CO;2-H.
We investigated whether percutaneous sensitization with different allergens through barrier-disrupted skin regulates the balance of Th1/Th2 cytokine expression. When mice were sensitized with the typical hapten picryl chloride (PiCl) by a single topical application to intact skin, there was an up-regulation in the lymph nodes (LN) of mRNA expression for the Th1 cytokines IL-2 or IFN-gamma, and for the Th2 cytokine IL-4. In contrast, sensitization with PiCl after barrier disruption of the skin down-regulated the expression of mRNA for IFN-gamma in a tape-stripping number-dependent manner without changing the expression of mRNA for IL-4. When mice were sensitized with house dust mite antigens (MA) by a single topical application to barrier-disrupted abdominal skin, there was a tape-stripping number-dependent up-regulation in the LN of mRNA expression for IL-4 but not for IL-2 or IFN-gamma. In the LN, mRNA for the IL-4-inducible immunoglobulins IgE and IgG1, but not for the IFN-gamma-inducible IgG2a, were up-regulated after sensitization with MA, while all three immunoglobulin mRNA were augmented after PiCl sensitization through intact skin. Antigenic elicitation by a topical application of PiCl in aural skin of mice sensitized through intact skin consistently increased the expression of mRNA for all three cytokines in the challenged skin, whereas elicitation in mice sensitized through barrier-disrupted skin decreased the expression of mRNA for IL-2 and IFN-gamma, but not for IL-4. Antigenic elicitation by subcutaneous injection of MA in aural skin consistently increased the expression of mRNA for IL-4, but not for IL-2 or IFN-gamma in the challenged skin. Infiltration of eosinophils in the dermis was more prominent following elicitation with MA in mice sensitized through barrier disruption than with PiCl in mice sensitized through intact skin. These findings suggest that the percutaneous entry of environmental allergens through barrier-disrupted skin is strongly associated with the induction of Th2-dominant immunological responses, as is seen in atopic dermatitis.
我们研究了通过屏障破坏的皮肤对不同变应原进行经皮致敏是否会调节Th1/Th2细胞因子表达的平衡。当通过单次局部应用将典型的半抗原苦味酸（PiCl）施用于完整皮肤对小鼠进行致敏时，Th1细胞因子IL-2或IFN-γ以及Th2细胞因子IL-4的淋巴结（LN）mRNA表达上调。相反，在皮肤屏障破坏后用PiCl致敏以胶带剥离次数依赖性方式下调了IFN-γ的mRNA表达，而未改变IL-4的mRNA表达。当通过单次局部应用将屋尘螨抗原（MA）施用于屏障破坏的腹部皮肤对小鼠进行致敏时，IL-4的LN mRNA表达呈胶带剥离次数依赖性上调，而IL-2或IFN-γ则不然。在LN中，用MA致敏后，IL-4诱导的免疫球蛋白IgE和IgG1的mRNA上调，而IFN-γ诱导的IgG2a的mRNA未上调，而通过完整皮肤用PiCl致敏后所有三种免疫球蛋白mRNA均增加。通过局部应用PiCl对经完整皮肤致敏的小鼠耳部皮肤进行抗原激发，始终会增加受攻击皮肤中所有三种细胞因子的mRNA表达，而对经屏障破坏皮肤致敏的小鼠进行激发则会降低IL-2和IFN-γ的mRNA表达，但不会降低IL-4的表达。通过皮下注射MA对耳部皮肤进行抗原激发，始终会增加受攻击皮肤中IL-4的mRNA表达，但不会增加IL-2或IFN-γ的表达。与通过完整皮肤致敏的小鼠用PiCl激发相比，通过屏障破坏致敏的小鼠用MA激发后，真皮中嗜酸性粒细胞的浸润更为明显。这些发现表明，环境变应原通过屏障破坏的皮肤经皮进入与Th2主导的免疫反应的诱导密切相关，如在特应性皮炎中所见。
