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胶带条在特应性皮炎和银屑病中检测到不同的免疫和屏障特征。

Tape strips detect distinct immune and barrier profiles in atopic dermatitis and psoriasis.

机构信息

Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory of Investigative Dermatology, The Rockefeller University, New York, NY.

Innovaderm Research, Montreal, Quebec, Canada.

出版信息

J Allergy Clin Immunol. 2021 Jan;147(1):199-212. doi: 10.1016/j.jaci.2020.05.048. Epub 2020 Jul 21.

Abstract

BACKGROUND

Our current understanding of atopic dermatitis (AD) and psoriasis pathophysiology is largely derived from skin biopsy studies that cause scarring and may be impractical in large-scale clinical trials. Although tape strips show promise as a minimally invasive technique in these common diseases, a comprehensive molecular profiling characterizing and differentiating the 2 diseases in tape strips is unavailable.

OBJECTIVE

Our aim was to construct a global transcriptome of tape strips from lesional and nonlesional skin of adults with moderate-to-severe AD and psoriasis.

METHODS

A total of 20 tape strips were obtained from lesional and nonlesional skin of patients with AD and psoriasis and skin from controls (n = 20 each); the strips were subjected to RNA sequencing (RNA-seq), with quantitative RT-PCR validation of immune and barrier biomarkers.

RESULTS

We detected RNA-seq profiles in 96 of 100 of samples (96%), with 4123 and 5390 genes differentially expressed in AD and psoriasis lesions versus in controls, respectively (fold change ≥ 2; false discovery rate [FDR] < 0.05). Nonlesional tape-stripped skin from patients with AD was more similar to lesional skin than to nonlesional skin of patients with psoriasis, which showed larger differentiation from lesions. AD and psoriasis tissues shared increases in levels of dendritic cell and T-cell markers (CD3, ITGAX/CD11c, and CD83), but AD tissues showed preferential T2 skewing (IL-13, CCL17/TARC, and CCL18), whereas psoriasis was characterized by higher levels of expression of T17-related (IL-17A/F and IL-36A/IL-36G), T1-related (IFN-γ and CXCL9/CXCL10), and innate immunity-related (nitric oxide synthase 2/inducible nitric oxide synthase and IL-17C) products (FDR < 0.05). Terminal differentiation (FLG2 and LCE5A), tight junction (CLDN8), and lipid biosynthesis and metabolism (FA2H and ALOXE3) products were significantly downregulated in both AD and psoriasis (FDR < 0.05). Nitric oxide synthase 2/inducible nitric oxide synthase expression (determined by quantitative PCR) differentiated AD and psoriasis with 100% accuracy.

CONCLUSION

RNA-seq tape strip profiling detected distinct immune and barrier signatures in lesional and nonlesional AD and psoriasis skin, suggesting their utility as a minimally invasive alternative to biopsies for detecting disease biomarkers.

摘要

背景

我们目前对特应性皮炎(AD)和银屑病发病机制的了解主要来自皮肤活检研究,这些研究会导致疤痕形成,并且在大规模临床试验中可能不切实际。虽然胶带条作为一种微创技术在这些常见疾病中具有很大的应用潜力,但尚无综合的分子谱分析可用于对这两种疾病进行特征描述和区分。

目的

我们旨在构建来自成人中度至重度 AD 和银屑病患者的病变和非病变皮肤的胶带条的全转录组。

方法

从 AD 和银屑病患者的病变和非病变皮肤以及对照者的皮肤中采集了总共 20 个胶带条(每组 20 个);对这些条带进行 RNA 测序(RNA-seq),并通过免疫和屏障生物标志物的定量 RT-PCR 进行验证。

结果

我们在 100 个样本中的 96 个样本(96%)中检测到了 RNA-seq 图谱,AD 病变与对照组相比,有 4123 个基因和银屑病病变与对照组相比,有 5390 个基因差异表达(倍数变化≥2;错误发现率[FDR]<0.05)。与银屑病患者的非病变皮肤相比,AD 患者的非病变胶带条皮肤与病变皮肤更相似,而与银屑病患者的非病变皮肤差异更大。AD 和银屑病组织中树突状细胞和 T 细胞标志物(CD3、ITGAX/CD11c 和 CD83)的水平均增加,但 AD 组织表现出 T2 向性(IL-13、CCL17/TARC 和 CCL18),而银屑病则以更高水平的 T17 相关(IL-17A/F 和 IL-36A/IL-36G)、T1 相关(IFN-γ 和 CXCL9/CXCL10)和先天免疫相关(一氧化氮合酶 2/诱导型一氧化氮合酶和 IL-17C)产物为特征(FDR<0.05)。角蛋白 2(FLG2)和丝聚蛋白 5(LCE5A)、紧密连接(CLDN8)以及脂质生物合成和代谢(鞘氨醇 1-磷酸酯合成酶 2/鞘氨醇 1-磷酸和脂肪酶 E3)产物在 AD 和银屑病中均显著下调(FDR<0.05)。用定量 PCR 确定的一氧化氮合酶 2/诱导型一氧化氮合酶表达可 100%准确地区分 AD 和银屑病。

结论

胶带条 RNA-seq 谱分析检测到 AD 和银屑病病变和非病变皮肤中独特的免疫和屏障特征,表明它们可用作活检的微创替代方法,用于检测疾病生物标志物。

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