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. 2024 Nov;79(11):3022-3035.
doi: 10.1111/all.16347. Epub 2024 Oct 14.

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

Claudia Carina Beerweiler  1   2 , Michael Salvermoser  1 , Johanna Theodorou  1   2 , Andreas Böck  1   3 , Franziska Sattler  1 , Paulina Kulig  4 , Vinko Tosevski  4 , Bianca Schaub  1   2   3
Affiliations

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

Claudia Carina Beerweiler et al. Allergy. 2024 Nov.

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.

Keywords: CyTOF; asthma; childhood; farming; protection.

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References

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