Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York 10065-6399, USA.
J Invest Dermatol. 2012 Jun;132(6):1615-26. doi: 10.1038/jid.2012.33. Epub 2012 Mar 8.
Psoriasis vulgaris is a complex disease characterized by alterations in growth and differentiation of epidermal keratinocytes, as well as a marked increase in leukocyte populations. Lesions are known to contain alterations in messenger RNAs encoding more than 1,000 products, but only a very small number of these transcripts has been localized to specific cell types or skin regions. In this study, we used laser capture microdissection (LCM) and gene array analysis to study the gene expression of cells in lesional epidermis (EPI) and dermis, compared with the corresponding non-lesional regions. Using this approach, we detected >1,800 differentially expressed gene products in the EPI or dermis of psoriasis lesions. These results established sets of genes that are differentially expressed between epidermal and dermal compartments, as well as between non-lesional and lesional psoriasis skin. One of our findings involved the local production of CCL19, a lymphoid-organizing chemokine, and its receptor CCR7 in psoriatic dermal aggregates, along with the presence of gene products LAMP3/DC-LAMP and CD83, which typify mature dendritic cells (DCs). Gene expression patterns obtained with LCM and microarray analysis along with T-cell and DC detection by immune staining suggest a possible mechanism for lymphoid organization via CCL19/CCR7 in diseased skin.
寻常型银屑病是一种复杂的疾病,其特征是表皮角质形成细胞的生长和分化改变,以及白细胞群体的显著增加。已知病变部位含有超过 1000 种产物的信使 RNA 改变,但只有极少数这些转录本被定位到特定的细胞类型或皮肤区域。在这项研究中,我们使用激光捕获显微切割 (LCM) 和基因芯片分析来研究病变表皮 (EPI) 和真皮中的细胞基因表达,与相应的非病变区域进行比较。使用这种方法,我们在银屑病病变的表皮或真皮中检测到 >1800 种差异表达的基因产物。这些结果确定了在表皮和真皮隔室之间以及非病变性和病变性银屑病皮肤之间差异表达的基因集。我们的发现之一涉及趋化因子 CCL19 的局部产生,CCL19 是一种淋巴器官组织趋化因子,其受体 CCR7 存在于银屑病真皮聚集物中,以及基因产物 LAMP3/DC-LAMP 和 CD83,这是成熟树突状细胞 (DC) 的典型特征。通过免疫染色检测 T 细胞和 DC,结合 LCM 和微阵列分析获得的基因表达模式表明,在疾病皮肤中,CCL19/CCR7 可能通过淋巴组织来实现。