Sage, Sophie E.; Leeb, Tosso; Jagannathan, Vidhya; Gerber, Vinzenz (2024). Single-cell profiling of bronchoalveolar cells reveals a Th17 signature in neutrophilic severe equine asthma. Immunology, 171(4), pp. 549-565. Wiley-Blackwell 10.1111/imm.13745
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Immunology_-_2023_-_Sage_-_Single_cell_profiling_of_bronchoalveolar_cells_reveals_a_Th17_signature_in_neutrophilic_severe.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (5MB) | Preview |
Severe equine asthma (SEA) is a complex respiratory condition characterized by chronic airway inflammation. It shares many clinical and pathological features with human neutrophilic asthma, making it a valuable model for studying this condition. However, the immune mechanisms driving SEA have remained elusive. Although SEA has been primarily associated with a Th2 response, there have also been reports of Th1, Th17, or mixed-mediated responses. To uncover the elusive immune mechanisms driving SEA, we performed single-cell mRNA sequencing (scRNA-seq) on cryopreserved bronchoalveolar cells from 11 Warmblood horses, 5 controls and 6 with SEA. We identified six major cell types, including B cells, T cells, monocytes–macrophages, dendritic cells, neutrophils, and mast cells. All cell types exhibited significant heterogeneity, with previously identified and novel cell subtypes. Notably, we observed monocyte–lymphocyte complexes and detected a robust Th17 signature in SEA, with CXCL13 upregulation in intermediate monocytes. Asthmatic horses exhibited expansion of the B-cell population, Th17 polarization of the T-cell populations, and dysregulation of genes associated with T-cell function. Neutrophils demonstrated enhanced migratory capacity and heightened aptitude for neutrophil extracellular trap formation. These findings provide compelling evidence for a predominant Th17 immune response in neutrophilic SEA, driven by dysregulation of monocyte and T-cell genes. The dysregulated genes identified through scRNA-seq have potential as biomarkers and therapeutic targets for SEA and provide insights into human neutrophilic asthma.
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