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.
Abstract: Inflammatory bowel disease (IBD) in horses is an idiopathic disorder, encompassing different types of chronic intestinal inflammation. The pathogenesis of the disease remains to be established, but it has been suggested that an imbalance between regulatory T cells (Tregs) and T helper 17 (Th17)-associated cytokines and altered toll-like receptor 4 (TLR4) expression is associated with intestinal inflammation in other species. The aim of the present study was to quantify Tregs in rectal biopsies from horses affected with IBD by immunohistochemistry and to evaluate expression of genes encoding interleukin (IL)-12p40, IL-17A, IL-23p19 and TLR4 by real-time quantitative PCR. Rectal biopsies from 11 healthy horses and 11 horses with clinical signs of IBD, showing inflammation classified as chronic simple proctitis (CSP) or chronic active simple proctitis (CASP), were evaluated. Expression of IL-17A mRNA was greater in horses affected with CASP compared with horses with CSP or healthy horses. In contrast, expression of IL-12p40 was lower in horses with CSP compared with horses with CASP or healthy horses. TLR4 expression was greater in horses with CASP compared with healthy horses. A positive correlation was seen between the numbers of Tregs and expression of IL-17A and IL-23p19. An association was demonstrated between the histopathological pattern of inflammation, cytokine profile and number of infiltrating Tregs. The research findings suggest that Th17 cells are involved in active IBD, possibly through recruitment of neutrophils via IL-17A, in combination with inadequate suppression of the inflammatory response by Tregs.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication Date: 2015-07-07 PubMed ID: 26346261DOI: 10.1016/j.tvjl.2015.07.003Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigates the role of certain immune cells and proteins in horses affected by Inflammatory Bowel Disease (IBD). Through examining rectal biopsies, the researchers found a correlation between the severity of IBD, an increased expression of certain genes, and an imbalance in the protective/regulatory immune cells.
Study Background
- Inflammatory Bowel Disease (IBD) is a chronic condition in horses characterised by ongoing intestinal inflammation. The exact cause of IBD in horses is yet to be identified.
- Previously, research has revealed a potential link between the disease and a disruption in the equilibrium of certain types of immune cells (Tregs and Th17).
- This study attempts to further investigate this link in horses, quantifying Tregs and evaluating the expression of certain genes in affected horses.
Methodology
- The study involved 11 healthy horses and 11 horses showing symptoms of IBD with varying severity of inflammation.
- Rectal biopsies were taken from each horse and analyzed. The researchers looked specifically for the presence and quantity of Tregs and examined the expression of genes encoding certain interleukins (IL-12p40, IL-17A, IL-23p19) and toll-like receptor 4 (TLR4).
- The quantification of Tregs was done by immunohistochemistry and the gene expression was evaluated by real-time quantitative PCR.
Key Findings
- The research showed that IL-17A gene expression was significantly higher in horses with more severe IBD. Conversely, IL-12p40 gene expression was lower in such horses.
- Similarly, TLR4 expression was greater in horses with more severe IBD compared to healthy horses.
- The study also found a positive correlation between the number of Tregs and the expression of IL-17A and IL-23p19 genes.
- Hence, the findings showed a clear correlation between inflammatory response as shown by gene expressions, the histopathological pattern of inflammation and the number of Tregs.
Implications of the Study
- These findings suggest that Th17 cells may play a vital role in the active state of IBD and can potentially recruit neutrophils via IL-17A.
- Furthermore, it suggests that the ongoing inflammation may be due to insufficient suppression by Tregs, thereby signifying an imbalance between inflammatory and regulatory immune response in horses with IBD.
- This study adds to the growing body of knowledge about the pathogenesis of IBD in horses and may help in the development of more targeted treatment strategies in the future.
Cite This Article
APA
Olofsson KM, Hjertner B, Fossum C, Press CM, Lindberg R.
(2015).
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.
Vet J, 206(1), 97-104.
https://doi.org/10.1016/j.tvjl.2015.07.003 Publication
Researcher Affiliations
- Department of Biomedical Sciences and Veterinary Public Health, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Ulls väg 26, Uppsala, Sweden. Electronic address: karin.olofsson@slu.se.
- Department of Biomedical Sciences and Veterinary Public Health, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Ulls väg 26, Uppsala, Sweden.
- Department of Biomedical Sciences and Veterinary Public Health, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Ulls väg 26, Uppsala, Sweden.
- Department of Basic Sciences and Aquatic Medicine, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Ullevålsveien 72, Oslo, Norway.
- Department of Biomedical Sciences and Veterinary Public Health, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Ulls väg 26, Uppsala, Sweden.
MeSH Terms
- Animals
- Biopsy / veterinary
- Cytokines / genetics
- Cytokines / metabolism
- Female
- Forkhead Transcription Factors / genetics
- Forkhead Transcription Factors / metabolism
- Gene Expression Regulation / physiology
- Horse Diseases / metabolism
- Horse Diseases / pathology
- Horses
- Inflammatory Bowel Diseases / metabolism
- Inflammatory Bowel Diseases / pathology
- Inflammatory Bowel Diseases / veterinary
- Male
- Th17 Cells / metabolism
- Toll-Like Receptor 4 / genetics
- Toll-Like Receptor 4 / metabolism
Citations
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