髓样树突状细胞全转录组分析揭示过敏患者中独特的遗传调控。

Whole Transcriptome Analysis of Myeloid Dendritic Cells Reveals Distinct Genetic Regulation in Patients with Allergies.

机构信息

Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, Seoul 02841, Korea.

Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Korea.

出版信息

Int J Mol Sci. 2020 Nov 16;21(22):8640. doi: 10.3390/ijms21228640.

Abstract

Dendritic cells (DCs) play critical roles in atopic diseases, orchestrating both innate and adaptive immune systems. Nevertheless, limited information is available regarding the mechanism through which DCs induce hyperresponsiveness in patients with allergies. This study aims to reveal novel genetic alterations and future therapeutic target molecules in the DCs from patients with allergies using whole transcriptome sequencing. Transcriptome sequencing of human BDCA-3+/CD11c+ DCs sorted from peripheral blood monocytes obtained from six patients with allergies and four healthy controls was conducted. Gene expression profile data were analyzed, and an ingenuity pathway analysis was performed. A total of 1638 differentially expressed genes were identified at -values < 0.05, with 11 genes showing a log2-fold change ≥1.5. The top gene network was associated with cell death/survival and organismal injury/abnormality. In validation experiments, amphiregulin (AREG) showed consistent results with transcriptome sequencing data, with increased mRNA expression in THP-1-derived DCs after Der p 1 stimulation and higher protein expression in myeloid DCs obtained from patients with allergies. This study suggests an alteration in the expression of DCs in patients with allergies, proposing related altered functions and intracellular mechanisms. Notably, might play a crucial role in DCs by inducing the Th2 immune response.

摘要

树突状细胞 (DCs) 在特应性疾病中发挥着关键作用,协调固有和适应性免疫系统。然而,关于 DC 如何诱导过敏患者产生高反应性的机制,目前信息有限。本研究旨在通过全转录组测序揭示过敏患者 DC 中的新的遗传改变和未来的治疗靶分子。对来自 6 名过敏患者和 4 名健康对照者外周血单核细胞中分离的人 BDCA-3+/CD11c+ DC 进行了全转录组测序。分析了基因表达谱数据,并进行了 Ingenuity 通路分析。鉴定到 1638 个差异表达基因,其 -值 < 0.05,有 11 个基因的对数倍变化≥1.5。顶级基因网络与细胞死亡/存活和机体损伤/异常有关。在验证实验中,表皮调节素 (AREG) 的结果与转录组测序数据一致,Der p 1 刺激后 THP-1 衍生的 DCs 中 mRNA 表达增加,过敏患者获得的髓样 DCs 中蛋白表达增加。本研究提示过敏患者 DC 表达发生改变,提出相关功能和细胞内机制改变。值得注意的是,可能通过诱导 Th2 免疫反应在 DCs 中发挥关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e08/7697962/354dc31b20ac/ijms-21-08640-g001.jpg

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