Farm-dust mediated protection of childhood asthma: Mass cytometry reveals novel cellular regulation

IF 12.6 1区医学 Q1 ALLERGY

Allergy Pub Date : 2024-10-14 DOI:10.1111/all.16347

Claudia Carina Beerweiler, Michael Salvermoser, Johanna Theodorou, Andreas Böck, Franziska Sattler, Paulina Kulig, Vinko Tosevski, Bianca Schaub

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Abstract

Background

Farm-dust mediated asthma protection in childhood was replicated in numerous epidemiological studies. Central immune mechanisms are not fully understood. This exploratory study aimed to disentangle underlying immunological regulation of farm-dust mediated protection in peripheral blood on a single-cell level.

Methods

Single-cell protein expression of in vitro farm-dust stimulated and unstimulated cells from allergic asthmatics and healthy controls were measured using mass cytometry. Analysis of innate and adaptive cellular proportions (linear regression) and T-cell proliferation was performed. Functional marker intensity was investigated using Earth Mover's Distance and the Monte Carlo permutation test.

Results

Farm-dust stimulation induced cell type-specific regulation: Key-features of farm-dust stimulation comprised opposing regulation of immune-cell frequencies (downregulated innate cell populations (monocytes/DCs (p < .001), NK-cells (p < .05)) and upregulated adaptive populations (B-cells, CD4⁺ T-cells (both p < .05)), reduced CD4⁺ CD25⁻ T-cell proliferation, and differential cell type-specific functional marker expression. Following stimulation, functional marker analysis revealed induced activation (CD25) in T-cells and NK-T-cells in both phenotypes even after correction for multiple testing. Cytotoxicity (GZMB) and inflammation (pERK1/2, pp38) related markers were reduced in T-cells exclusively in asthmatic children. Asthma-associated markers (Gata3, RORγ, and HLA-DR) were reduced in T- and innate- cell populations of asthmatics following stimulation. B-cells displayed a phenotypically independent increase of diverse functional markers upon farm-dust stimulation.

Conclusions

This study mimicking in vivo environmental exposure identified a novel profile of immune-regulatory markers using mass cytometry demonstrating decreased asthma-associated markers following farm-dust stimulation. These findings may be key for further studies on asthma prevention in childhood.

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农场粉尘介导的儿童哮喘保护：质谱仪揭示了新的细胞调控。

背景许多流行病学研究都证实了农场粉尘介导的儿童哮喘保护作用。中枢免疫机制尚不完全清楚。这项探索性研究旨在从单细胞水平上揭示农用粉尘介导的外周血保护作用的潜在免疫调节机制。方法使用质谱细胞计数法测量过敏性哮喘患者和健康对照组体外农用粉尘刺激细胞和未刺激细胞的单细胞蛋白表达。对先天性和适应性细胞比例（线性回归）以及 T 细胞增殖进行了分析。使用地球移动距离和蒙特卡罗置换检验对功能标记强度进行了研究：农田粉尘刺激的主要特征包括对免疫细胞频率的相反调节（先天性细胞群（单核细胞/DCs（p < .001）、NK 细胞（p < .05））下调，适应性细胞群（B 细胞、CD4+ T 细胞（两者均 p < .05））上调，CD4+ CD25- T 细胞增殖减少，以及细胞类型特异性功能标记表达不同。刺激后，功能标记分析表明，即使经过多重测试校正，两种表型的 T 细胞和 NK-T 细胞的诱导活化（CD25）仍然存在。细胞毒性（GZMB）和炎症（ppERK1/2、pp38）相关标记物在 T 细胞中减少，只有在哮喘患儿中才会出现。哮喘患者的 T 细胞和先天性细胞群在受到刺激后，哮喘相关标记物（Gata3、RORγ 和 HLA-DR）减少。结论：这项模拟体内环境暴露的研究利用质谱仪确定了免疫调节标志物的新特征，表明农场粉尘刺激后哮喘相关标志物减少。这些发现可能是进一步研究预防儿童哮喘的关键。

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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来源期刊

Allergy 医学-过敏

CiteScore

26.10

自引率

9.70%

发文量

393

审稿时长

2 months

期刊介绍： Allergy is an international and multidisciplinary journal that aims to advance, impact, and communicate all aspects of the discipline of Allergy/Immunology. It publishes original articles, reviews, position papers, guidelines, editorials, news and commentaries, letters to the editors, and correspondences. The journal accepts articles based on their scientific merit and quality. Allergy seeks to maintain contact between basic and clinical Allergy/Immunology and encourages contributions from contributors and readers from all countries. In addition to its publication, Allergy also provides abstracting and indexing information. Some of the databases that include Allergy abstracts are Abstracts on Hygiene & Communicable Disease, Academic Search Alumni Edition, AgBiotech News & Information, AGRICOLA Database, Biological Abstracts, PubMed Dietary Supplement Subset, and Global Health, among others.