Expression of T helper type 17 (Th17)-associated cytokines and toll-like receptor 4 and their correlation with Foxp3 positive cells in rectal biopsies of horses with clinical signs of inflammatory bowel disease.
Authors: Olofsson Karin M, Hjertner Bernt, Fossum Caroline, Press Charles M, Lindberg Ronny
Journal: Veterinary journal (London, England : 1997)
Summary
Equine inflammatory bowel disease remains poorly understood, though research in other species suggests dysregulation of immune tolerance mechanisms—specifically an imbalance between regulatory T cells (Tregs) and pro-inflammatory T helper 17 (Th17) responses—may underpin chronic intestinal inflammation. Karin Olofsson and colleagues examined rectal biopsies from 11 healthy horses and 11 with clinical IBD, quantifying Foxp3+ Tregs via immunohistochemistry and measuring mRNA expression of key Th17-associated cytokines (IL-17A, IL-12p40, IL-23p19) and toll-like receptor 4 using qPCR. Horses with the most severe inflammation (chronic active simple proctitis, CASP) showed significantly elevated IL-17A and TLR4 expression compared to those with milder chronic simple proctitis (CSP) or healthy controls, whilst IL-12p40 was paradoxically reduced in CSP cases; intriguingly, Treg numbers correlated positively with both IL-17A and IL-23p19 expression, suggesting these regulatory cells accumulate in response to active inflammation but may be functionally compromised. These findings indicate that active equine IBD involves Th17-driven pathology—likely operating through IL-17A-mediated neutrophil recruitment—coupled with inadequate immune suppression, implying that therapeutic strategies targeting Treg function or IL-17 signalling warrant investigation. For practitioners, this work underscores that IBD severity exists on a spectrum with distinct immunological signatures, potentially guiding future diagnostic refinement and personalised treatment approaches beyond current empirical management.
Read the full abstract on PubMed
Practical Takeaways
- •IBD in horses appears to involve Th17-mediated inflammation with neutrophil recruitment via IL-17A, which could inform future targeted treatment strategies beyond current supportive management
- •The imbalance between regulatory T cells and pro-inflammatory cytokines suggests potential therapeutic targets; however, rectal biopsy remains necessary for definitive diagnosis and inflammatory classification
- •Understanding the immune mechanism may help explain variable responses to treatment and guide development of immunomodulatory therapies for chronic intestinal inflammation in horses
Key Findings
- •IL-17A mRNA expression was significantly greater in horses with CASP compared to CSP or healthy controls
- •IL-12p40 expression was lower in horses with CSP compared to CASP or healthy horses
- •TLR4 expression was greater in horses with CASP versus healthy horses
- •Positive correlation demonstrated between regulatory T cell numbers and IL-17A and IL-23p19 expression, suggesting inadequate immune suppression in active disease