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扁桃体转录组谱在特应性和非特应性受试者中的差异。

Tonsillar transcriptional profiles in atopic and non-atopic subjects.

机构信息

Department of Pediatrics and Adolescent Medicine, University of Turku, Turku, Finland.

Haartman Institute, University of Helsinki, Helsinki, Finland.

出版信息

Allergy. 2023 Feb;78(2):522-536. doi: 10.1111/all.15458. Epub 2022 Aug 10.

Abstract

BACKGROUND

Emerging research suggests that local lymphatic tissue such as tonsils have important role in regulating the immune responses. However, allergen sensitization-induced alterations in transcriptome of tonsils are not known.

OBJECTIVES

To examine the key differences in tonsillar gene expression between atopic and non-atopic subjects and further by type of sensitization.

METHODS

RNA-sequencing was performed on 52 tonsillar samples from atopic and non-atopic tonsillectomy patients. Sensitization to common food- and aero-allergen was defined by allergen specific IgE. Following groups were studied: (1) aero- and food-allergen sensitized (AS+FS) versus non-sensitized (NS), (2) aeroallergen-sensitized (AS) versus food-allergen sensitized (FS), (3) AS versus NS, (4) FS versus NS. Bioinformatics analysis was done using DESeq2(v3.10.2), WGCNA and GATK pipeline in R software (v3.3.1). Protein-protein interaction network was made from String database.

RESULTS

We studied 13 aeroallergen-sensitized, 6 food-allergen sensitized, 4 both food-and aero-allergen-sensitized and 29 non-sensitized tonsillectomy patients. Overall, 697 unique differentially expressed genes (DEGs) were detected in all sensitized subgroups including chemokines (CXCL2, CXCL8, CXCL10, CXCL11), IL-20RA, MUC1 and MUC20. When comparing different groups, the gene expression profiles overlapped except the AS versus FS group comparison, suggesting significantly different gene expression between the two sensitization subgroups. Furthermore, aeroallergen-sensitized subjects had more prominent immune responses compared with non-sensitized and food-allergen sensitized subjects including gene expression for IL-17 pathway and Toll-like receptor signalling pathway.

CONCLUSION

Allergic sensitization is associated with extensive tonsillar transcriptomic alterations and changes in immune related genes and pathways. Distinct differences were found between aero-allergen and food-allergen sensitization.

摘要

背景

新兴研究表明,扁桃体等局部淋巴组织在调节免疫反应方面具有重要作用。然而,过敏原致敏诱导的扁桃体转录组变化尚不清楚。

目的

研究过敏性和非过敏性扁桃体切除术患者扁桃体基因表达的关键差异,并进一步按致敏类型进行研究。

方法

对 52 例过敏性和非过敏性扁桃体切除术患者的扁桃体样本进行 RNA 测序。过敏原特异性 IgE 定义了对常见食物和空气过敏原的致敏。研究了以下几组:(1)空气和食物过敏原致敏(AS+FS)与非致敏(NS),(2)空气过敏原致敏(AS)与食物过敏原致敏(FS),(3)AS 与 NS,(4)FS 与 NS。使用 DESeq2(v3.10.2)、WGCNA 和 GATK 管道在 R 软件(v3.3.1)中进行生物信息学分析。蛋白质-蛋白质相互作用网络来自 String 数据库。

结果

我们研究了 13 例空气过敏原致敏、6 例食物过敏原致敏、4 例空气和食物过敏原致敏和 29 例非致敏扁桃体切除术患者。总体而言,在所有致敏亚组中检测到 697 个独特的差异表达基因(DEG),包括趋化因子(CXCL2、CXCL8、CXCL10、CXCL11)、IL-20RA、MUC1 和 MUC20。当比较不同组时,除了 AS 与 FS 组的比较外,基因表达谱重叠,表明这两个致敏亚组之间的基因表达存在显著差异。此外,空气过敏原致敏患者与非致敏和食物过敏原致敏患者相比,具有更明显的免疫反应,包括 IL-17 途径和 Toll 样受体信号通路的基因表达。

结论

过敏致敏与扁桃体转录组的广泛改变以及与免疫相关的基因和途径有关。空气过敏原和食物过敏原致敏之间存在明显差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7f5/10087516/1e7dad3deaea/ALL-78-522-g005.jpg

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