Molecular profiling and gene expression analysis in cutaneous sarcoidosis: The role of interleukin-12, interleukin-23, and the T-helper 17 pathway
Molecular profiling and gene expression analysis in cutaneous sarcoidosis: The role of interleukin-12, interleukin-23, and the T-helper 17 pathway
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DOI：
10.1016/j.jaad.2011.06.017
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发表时间：
2012-06-01
影响因子：
13.8
通讯作者：
Brodmerkel, Carrie
中科院分区：
文献类型：
--
作者：
Judson, Marc A.;Marchell, Richard M.;Brodmerkel, Carrie
背景：皮肤结节病（CS）皮肤为肉芽肿性结节病组织提供了相对无创的通道。目的：探讨辅助性t (Th) 1和Th17通路在结节病中的作用。方法：采用分子分析和基因表达分析方法，对CS中Th1、Th17等免疫介导通路进行分析。从结节病皮肤病变（病变皮肤[LS]）、CS患者未受影响的皮肤（非LS）和健康对照者的皮肤中获得分子谱。采集全血，比较结节病皮损与全血的分子谱。结果：20名参与者入组：15名活跃的CS和5名健康志愿者。微阵列分析显示，非LS和健康志愿者皮肤与LS的数千个基因差异表达（>= 2倍的变化错误发现率，P < 0.01）。靶向选择与Th1和Th17表型相关的基因显示，结节病的Th1基因谱和白细胞介素(IL)-23和IL- 23r的表达较强，而其他Th17途径基因的表达有限。IL-21和转录信号传导激活因子3 （STAT3）在皮肤和全血中也出现了异常，这为IL-12通路的参与和Th17通路的潜在激活提供了额外的证据。局限性：测量是在单一时间点进行的，可能无法确定可能在纵向随访患者中确定的机制。结论：这些发现对结节病发病机制中可能涉及的失调通路提供了新的见解。[J] .中华皮肤科杂志，2012;66:901-10。
Background: Cutaneous sarcoidosis (CS) skin provides relatively noninvasive access to granulomatous sarcoidosis tissue.Objective: We sought to explore the role of the T-helper (Th) 1 and Th17 pathways in sarcoidosis.Methods: We used molecular profiling and gene expression analysis to analyze the Th1 and Th17 pathways and other immune-mediated pathways in CS. Molecular profiles were obtained from sarcoidosis skin lesions (lesional skin [LS]), unaffected skin from patients with CS (non-LS), and the skin of healthy control subjects. Whole blood was collected to compare the molecular profile of sarcoidosis skin lesions and whole blood.Results: Twenty participants were enrolled: 15 with active CS and 5 healthy volunteers. Microarray analyses comparing non-LS and healthy volunteer skin with LS showed several thousand genes differentially expressed (>= 2-fold change false discovery rate, P < .01). Targeted selections of genes associated with Th1 and Th17 phenotypes showed a strong Th1 profile of sarcoidosis and expression of interleukin (IL)-23 and IL-23R with limited expression of other Th17 pathway genes. IL-21 and signal transducer and activator of transcription 3 (STAT3) were also dysregulated in skin and whole blood, providing additional evidence for involvement of the IL-12 pathway and potential activation of the Th17 pathway.Limitations: Measurements were made at a single point in time and may not identify mechanisms that may be identified in patients followed up longitudinally.Conclusion: These findings provide novel insight into the dysregulated pathways that may be involved in the pathogenesis of sarcoidosis. (J Am Acad Dermatol 2012;66:901-10.)