Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma.
Authors: Pacholewska Alicja, Jagannathan Vidhya, Drögemüller Michaela, Klukowska-Rötzler Jolanta, Lanz Simone, Hamza Eman, Dermitzakis Emmanouil T, Marti Eliane, Leeb Tosso, Gerber Vincent
Journal: PloS one
Summary
# Equine Asthma and Immune Cell Dysfunction: New Genetic Insights Recurrent airway obstruction (RAO) in horses mirrors human asthma both clinically and immunologically, with hay dust triggering exacerbations in susceptible animals, yet the underlying genetic mechanisms driving this heightened immune sensitivity remained poorly understood. Researchers analysed gene expression profiles in peripheral blood mononuclear cells (PBMCs) from 85 horses (40 RAO-affected, 45 controls) using RNA sequencing across three different horse populations; samples were stimulated with hay dust extract, lipopolysaccharides, parasite antigen, or left unstimulated, yielding 561 individual expression datasets. The most striking finding was marked upregulation of CXCL13—a chemokine involved in immune cell trafficking—alongside dysregulation of genes controlling cell cycle progression, particularly CDC20, when RAO-affected horses' PBMCs were exposed to hay dust; expression changes also involved hypoxia-inducible factor (HIF-1) target genes. These systemic immune alterations suggest that RAO-susceptible horses have fundamental defects in how their immune cells proliferate and migrate in response to environmental triggers, pointing toward potential therapeutic targets beyond simple allergen avoidance. For practitioners, these findings underscore that RAO represents a complex genetic predisposition affecting systemic immune regulation rather than a localised airway problem alone, with implications for understanding why management interventions vary in effectiveness between individual horses.
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Practical Takeaways
- •RAO involves systemic immune dysregulation affecting cell trafficking and proliferation, not just local airway inflammation—management should address environmental triggers comprehensively
- •Individual horses may show different immune responses depending on genetic background and specific environmental exposures (hay dust vs. other allergens)
- •Understanding the molecular basis of RAO supports the rationale for environmental management (hay quality, dust reduction) as primary prevention strategy
Key Findings
- •Significant differential gene expression profiles in PBMCs from RAO-affected horses compared to controls, with strongest differences upon hay dust extract stimulation
- •Strong upregulation of CXCL13 and multiple cell cycle regulation genes in stimulated samples from RAO horses
- •Altered expression of HIF-1 transcription factor target genes in RAO-affected horses
- •Cell cycle regulator CDC20 identified as important in immune response dysregulation in RAO