Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Columbia University College of Physicians & Surgeons, New York, NY.
Department of Dermatology, Tel-Hashomer, Tel Aviv, Israel.
J Allergy Clin Immunol. 2014 Aug;134(2):362-72. doi: 10.1016/j.jaci.2014.03.009. Epub 2014 Apr 25.
Allergic contact dermatitis (ACD) is the most common occupational disease. Although murine contact hypersensitivity provides a framework for understanding ACD, it carries important differences from its human counterpart. Unlike the contact hypersensitivity model, which is induced by potent sensitizers (ie, dinitrofluorobenzene), human ACD is induced by weak-to-moderate sensitizers (ie, nickel), which cannot induce reactions in mice. Distinct hapten-specific immune-polarizing responses to potent inducers were suggested in mice, with unclear relevance to human ACD.
We explored the possibility of distinct T-cell polarization responses in skin to common clinically relevant ACD allergens.
Gene-expression and cellular studies were performed on common allergens (ie, nickel, fragrance, and rubber) compared with petrolatum-occluded skin, using RT-PCR, gene arrays, and immunohistochemistry.
Despite similar clinical reactions in all allergen groups, distinct immune polarizations characterized different allergens. Although the common ACD transcriptome consisted of 149 differentially expressed genes across all allergens versus petrolatum, a much larger gene set was uniquely altered by individual allergens. Nickel demonstrated the highest immune activation, with potent inductions of innate immunity, TH1/TH17 and a TH22 component. Fragrance, and to a lesser extent rubber, demonstrated a strong TH2 bias, some TH22 polarization, and smaller TH1/TH17 contributions.
Our study offers new insights into the pathogenesis of ACD, expanding the understanding of T-cell activation and associated cytokines in allergen-reactive tissues. It is the first study that defines the common transcriptome of clinically relevant sensitizers in human skin and identifies unique pathways preferentially activated by different allergens, suggesting that ACD cannot be considered a single entity.
过敏性接触性皮炎（ACD）是最常见的职业病。尽管小鼠接触超敏反应为理解 ACD 提供了一个框架，但它与人类对应物存在重要差异。与由强敏化剂（如二硝基氟苯）诱导的接触超敏反应模型不同，人类 ACD 由弱至中等强度的敏化剂（如镍）诱导，而这些敏化剂不能在小鼠中诱导反应。在小鼠中，对强诱导剂有独特的半抗原特异性免疫极化反应，其与人类 ACD 的相关性尚不清楚。
我们探讨了常见临床相关 ACD 过敏原在皮肤中是否存在独特的 T 细胞极化反应的可能性。
采用 RT-PCR、基因芯片和免疫组织化学方法，对常见过敏原（如镍、香料和橡胶）与凡士林封闭皮肤进行基因表达和细胞研究。
尽管所有过敏原组的临床反应相似，但不同的免疫极化特征区分了不同的过敏原。尽管常见的 ACD 转录组由所有过敏原与凡士林相比的 149 个差异表达基因组成，但个体过敏原还会特异性地改变更大的基因集。镍表现出最高的免疫激活，强烈诱导固有免疫、TH1/TH17 和 TH22 成分。香料，以及在较小程度上的橡胶，表现出强烈的 TH2 偏向，一些 TH22 极化，以及较小的 TH1/TH17 贡献。
我们的研究为 ACD 的发病机制提供了新的见解，扩展了对变应原反应组织中 T 细胞激活和相关细胞因子的理解。这是第一项定义临床上相关敏化剂在人类皮肤中的共同转录组并确定不同过敏原优先激活的独特途径的研究，表明 ACD 不能被视为单一实体。
