RNA Sequencing Analysis of Monocytes Exposed to Airway Fluid From Children With Pediatric Acute Respiratory Distress Syndrome.

Q4 Medicine Critical care explorations Pub Date : 2024-10-04 eCollection Date: 2024-10-01 DOI:10.1097/CCE.0000000000001125
Jocelyn R Grunwell, Min Huang, Susan T Stephenson, Mallory Tidwell, Michael J Ripple, Anne M Fitzpatrick, Rishikesan Kamaleswaran
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引用次数: 0

Abstract

Objectives: Monocytes are plastic cells that assume different polarization states that can either promote inflammation or tissue repair and inflammation resolution. Polarized monocytes are partially defined by their transcriptional profiles that are influenced by environmental stimuli. The airway monocyte response in pediatric acute respiratory distress syndrome (PARDS) is undefined. To identify differentially expressed genes and networks using a novel transcriptomic reporter assay with donor monocytes exposed to the airway fluid of intubated children with and at-risk for PARDS. To determine differences in gene expression at two time points using the donor monocyte assay exposed to airway fluid from intubated children with PARDS obtained 48-96 hours following initial tracheal aspirate sampling.

Design: In vitro pilot study carried out using airway fluid supernatant.

Setting: Academic 40-bed PICU.

Participants: Fifty-seven children: 44 children with PARDS and 13 children at-risk for PARDS.

Interventions: None.

Measurements and main results: We performed bulk RNA sequencing using a transcriptomic reporter assay of monocytes exposed to airway fluid from intubated children to discover gene networks differentiating PARDS from at-risk for PARDS and those differentiating mild/moderate from severe PARDS. We also report differences in gene expression in children with PARDS 48-96 hours following initial tracheal aspirate sampling. We found that interleukin (IL)-10, IL-4, and IL-13, cytokine/chemokine signaling, and the senescence-associated secretory phenotype are upregulated in monocytes exposed to airway fluid from intubated children with PARDS compared with those at-risk for PARDS. Signaling by NOTCH, histone deacetylation/acetylation, DNA methylation, chromatin modifications (B-WICH complex), and RNA polymerase I transcription and its associated regulatory apparatus were upregulated in children with PARDS 48-96 hours following initial tracheal aspirate sampling.

Conclusions: We identified gene networks important to the PARDS airway immune response using bulk RNA sequencing from a monocyte reporter assay that exposed monocytes to airway fluid from intubated children with and at-risk for PARDS. Mechanistic investigations are needed to validate our findings.

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对暴露于小儿急性呼吸窘迫综合征患儿气道液的单核细胞进行 RNA 测序分析。
目的:单核细胞是一种可塑性细胞,可呈现不同的极化状态,既可促进炎症,也可促进组织修复和炎症消退。极化的单核细胞受环境刺激的影响,其转录谱可对其进行部分定义。小儿急性呼吸窘迫综合征(PARDS)中气道单核细胞的反应尚未明确。使用一种新型转录组报告分析法,对暴露于插管的 PARDS 患儿和高危 PARDS 患儿气道液中的供体单核细胞进行分析,以确定差异表达的基因和网络。使用供体单核细胞检测法确定暴露于首次气管抽吸取样后 48-96 小时内插管的 PARDS 患儿气道液的供体单核细胞在两个时间点的基因表达差异:设计:使用气道液上清液进行体外试验研究:环境:拥有 40 张病床的学术性 PICU:57名儿童:干预措施:无:测量和主要结果我们使用转录组报告分析法对暴露于插管儿童气道液的单核细胞进行了大量 RNA 测序,以发现区分 PARDS 和 PARDS 高危人群的基因网络,以及区分轻度/中度 PARDS 和重度 PARDS 的基因网络。我们还报告了 PARDS 患儿在初次气管抽吸取样 48-96 小时后的基因表达差异。我们发现,与 PARDS 高危人群相比,暴露于 PARDS 插管儿童气道液的单核细胞中的白细胞介素 (IL)-10、IL-4 和 IL-13、细胞因子/趋化因子信号转导以及衰老相关分泌表型均上调。在首次气管抽吸取样 48-96 小时后,NOTCH 信号、组蛋白去乙酰化/乙酰化、DNA 甲基化、染色质修饰(B-WICH 复合物)和 RNA 聚合酶 I 转录及其相关调节装置在 PARDS 患儿中上调:结论:我们利用单核细胞报告实验中的大量 RNA 测序,将单核细胞暴露于插管的 PARDS 患儿和 PARDS 高危患儿的气道液中,发现了对 PARDS 气道免疫反应很重要的基因网络。要验证我们的发现,还需要进行机制研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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CiteScore
5.70
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0.00%
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审稿时长
8 weeks
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