Interleukin-17A pathway target genes are upregulated in Equus caballus supporting limb laminitis.
Authors: Cassimeris Lynne, Engiles Julie B, Galantino-Homer Hannah
Journal: PloS one
Summary
Supporting limb laminitis (SLL) represents a devastating secondary complication following orthopedic injury or infection, yet its underlying inflammatory mechanisms remain incompletely understood; this research investigated whether the interleukin-17A (IL-17A) signalling pathway—known to mediate both healing and pathological skin responses in other tissues—is activated in lamellar tissue during SLL. The authors isolated lamellar samples from Thoroughbreds euthanised with naturally occurring SLL and compared gene expression profiles to age- and breed-matched controls using RT-PCR and quantitative qPCR, supplemented by in situ hybridisation and immunofluorescence to localise protein expression. Remarkably, IL-17A itself was predominantly detectable only in laminitic tissue, whilst 11 measured IL-17A target genes showed dramatic upregulation in SLL samples; specifically, DEFB4B and S100A9 (calprotectin components) were expressed 15–100 fold higher in severe acute cases and 15–200 fold higher in severe chronic laminitis compared with controls, with even developmental/subclinical cases showing approximately 5-fold elevation. These genes were expressed in suprabasal keratinocytes of affected lamellar tissue, suggesting the lamellae mount a comparable stress-response to that characterised in other epidermal tissues. Understanding that SLL involves IL-17A pathway activation opens therapeutic avenues for targeted anti-inflammatory intervention—potential candidates include IL-17A antagonists or selective targeting of downstream effectors like calprotectin—which might interrupt the cascade of lamellar inflammation and tissue destruction before irreversible damage occurs.
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Practical Takeaways
- •Understanding IL-17A pathway activation in SLL may lead to new therapeutic targets for anti-inflammatory intervention beyond current treatment options
- •The consistent upregulation of specific genes (DEFB4B, S100A9) across different SLL severity stages suggests these could become biomarkers for disease diagnosis or monitoring
- •Supporting limb laminitis involves a specific molecular inflammatory cascade similar to human skin stress responses, which could accelerate translation of human dermatological therapies to equine medicine
Key Findings
- •IL-17A was primarily detectable in laminitic lamellar tissues but absent in non-laminitic controls
- •DEFB4B and S100A9 genes were upregulated 15-100 fold in severe acute SLL compared to controls
- •All IL-17A target genes except CCL20 were expressed in laminitic samples, but undetectable in non-laminitic samples
- •Gene expression occurred primarily in suprabasal keratinocytes of lamellar tissue, demonstrating IL-17A pathway activation in response to lamellar stress