Laboratory for Investigative Dermatology, Rockefeller University, New York, NY 10065, USA.
J Allergy Clin Immunol. 2009 Dec;124(6):1235-1244.e58. doi: 10.1016/j.jaci.2009.09.031.
Psoriasis and atopic dermatitis (AD) are common, complex inflammatory skin diseases. Both diseases display immune infiltrates in lesions and epidermal growth/differentiation alterations associated with a defective skin barrier. An incomplete understanding of differences between these diseases makes it difficult to compare human disease pathology to animal disease models.
To characterize differences between these diseases in expression of genes related to epidermal growth/differentiation and inflammatory circuits.
We performed genomic profiling of mRNA in chronic psoriasis (n = 15) and AD (n = 18) skin lesions compared with normal human skin (n = 15).
As expected, clear disease classifications could be constructed on the basis of expected immune polarity (T(H)1, T(H)2, T(H)17) differences. However, even more striking differences were identified in epidermal differentiation programs that could be used for precise disease classifications. Although both psoriasis and AD skin lesions displayed regenerative epidermal hyperplasia, which is a general alteration in epidermal growth, keratinocyte terminal differentiation was differentially polarized. In AD, we found selective defects in expression of multiple genes encoding the cornified envelope, with the largest alteration in loricrin (expressed at 2% of the level of normal skin). At the ultrastructural level, the cornified envelope in AD was broadly defective with highly decreased compaction of corneocytes and reduced intercellular lipids. Hence, the entire keratinocyte terminal differentiation program (cytoplasmic compaction, cornification, and lipid release) is defective in AD, potentially underlying the immune differences.
Our study shows that although alterations in barrier responses exist in both diseases, epidermal differentiation is differentially polarized, with major implications for primary disease pathogenesis.
银屑病和特应性皮炎（AD）是常见的、复杂的炎症性皮肤病。这两种疾病在病变部位均表现出免疫浸润和表皮生长/分化改变，与皮肤屏障缺陷有关。由于对这些疾病之间的差异认识不足，使得难以将人类疾病的病理学与动物疾病模型进行比较。
描述与表皮生长/分化和炎症回路相关的基因在这两种疾病中的表达差异。
我们对慢性银屑病（n=15）和 AD（n=18）皮损与正常皮肤（n=15）的 mRNA 进行了基因组谱分析。
正如预期的那样，基于预期的免疫极性（TH1、TH2、TH17）差异，可以构建明确的疾病分类。然而，在表皮分化程序中还发现了更明显的差异，这些差异可用于精确的疾病分类。尽管银屑病和 AD 皮损均显示出再生性表皮过度增生，这是表皮生长的一般改变，但角蛋白细胞终末分化呈不同的极化。在 AD 中，我们发现多个编码角蛋白细胞包膜的基因表达选择性缺陷，其中丝聚蛋白的改变最大（表达水平仅为正常皮肤的 2%）。在超微结构水平上，AD 中的角蛋白细胞包膜广泛缺陷，导致角蛋白细胞的紧密性降低，细胞间脂质减少。因此，AD 中整个角蛋白细胞终末分化程序（细胞质浓缩、角化和脂质释放）均存在缺陷，这可能是免疫差异的基础。
我们的研究表明，尽管这两种疾病均存在屏障反应改变，但表皮分化呈不同的极化，这对主要的疾病发病机制有重要影响。
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