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Veterinary journal (London, England : 1997)2014; 202(3); 516-521; doi: 10.1016/j.tvjl.2014.09.003

Increased FOXP3 expression in tumour-associated tissues of horses affected with equine sarcoid disease.

Abstract: Recent studies suggest that regulatory T cells (Tregs) are associated with disease severity and progression in papilloma virus induced neoplasia. Bovine papilloma virus (BPV) is recognised as the most important aetiological factor in equine sarcoid (ES) disease. The aim of this study was to compare expression levels of Treg markers and associated cytokines in tissue samples of ES-affected equids with skin samples of healthy control horses. Eleven ES-affected, and 12 healthy horses were included in the study. Expression levels of forkhead box protein 3 (FOXP3), interleukin 10 (IL10), interleukin 4 (IL4) and interferon gamma (IFNG) mRNA in lesional and tumour-distant samples from ES-affected horses, as well as in dermal samples of healthy control horses were measured using quantitative reverse transcription polymerase chain reaction (PCR). Expression levels were compared between lesional and tumour-distant as well as between tumour-distant and control samples. Furthermore, BPV-1 E5 DNA in samples of ES-affected horses was quantified using quantitative PCR, and possible associations of viral load, disease severity and gene expression levels were evaluated. Expression levels of FOXP3, IL10 and IFNG mRNA and BPV-1 E5 copy numbers were significantly increased in lesional compared to tumour-distant samples. There was no difference in FOXP3 and cytokine expression in tumour-distant samples from ES- compared with control horses. In tumour-distant samples viral load was positively correlated with IL10 expression and severity score. The increased expression of Treg markers in tumour-associated tissues of ES-affected equids indicates a local, Treg-induced immune suppression.
Publication Date: 2014-09-06 PubMed ID: 25266649DOI: 10.1016/j.tvjl.2014.09.003Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This study provides insights into the functioning of T regulatory cells in the progression of papilloma virus-induced neoplasia. It focuses on the Bovine Papilloma Virus (BPV), the primary cause of equine sarcoid (ES) disease in horses. The researchers observed that Treg markers and associated cytokines show higher expression in ES-affected horses when compared to healthy ones.

Study Setup

  • The researchers designed this study to compare the expression levels of Treg markers and associated cytokines in ES-affected horses with that of healthy control horses. The Treg markers in focus were the forkhead box protein 3 (FOXP3), interleukin 10 (IL10), interleukin 4 (IL4), and interferon gamma (IFNG).
  • The study was conducted on 11 ES-affected horses and 12 healthy ones. The researchers assessed the mRNA expression levels of FOXP3, IL10, IL4, and IFNG in lesional (tumour site) and non-lesional (tumour-distant) samples taken from the ES-affected horses, and dermal samples from the healthy horses.
  • The researchers used quantitative reverse transcription polymerase chain reaction (PCR) to measure these expression levels and compare them among lesional and non-lesional samples, and between non-lesional and control samples.
  • In addition to this, the team also quantified the BPV-1 E5 DNA in the samples from ES-affected horses using quantitative PCR method. They further analysed the potential associations between viral load (quantity of BPV-1 E5 DNA), disease severity, and gene expression levels.

Findings

  • The researchers found that the mRNA expression levels of FOXP3, IL10, and IFNG, and the BPV-1 E5 copy numbers were significantly higher in lesional samples compared to non-lesional ones.
  • Interestingly, no difference was observed in the expression levels of FOXP3 and cytokines in non-lesional samples taken from ES-affected horses and those taken from control horses.
  • In non-lesional samples, they found a positive correlation between viral load, IL10 expression, and severity score, indicating these factors potentially increase in tandem.

Conclusion

  • This research concluded that the increased expression of Treg markers in tumour-associated tissues of ES-affected horses points to a local immune suppression influenced by Tregs.
  • This finding enhances the understanding of T regulatory cells’ role in papilloma virus-induced neoplasia, giving more depth to the knowledge needed for designing effective therapeutic strategies.

Cite This Article

APA
Mählmann K, Hamza E, Marti E, Dolf G, Klukowska J, Gerber V, Koch C. (2014). Increased FOXP3 expression in tumour-associated tissues of horses affected with equine sarcoid disease. Vet J, 202(3), 516-521. https://doi.org/10.1016/j.tvjl.2014.09.003

Publication

ISSN: 1532-2971
NlmUniqueID: 9706281
Country: England
Language: English
Volume: 202
Issue: 3
Pages: 516-521
PII: S1090-0233(14)00372-4

Researcher Affiliations

Mählmann, K
  • Swiss Institute of Equine Medicine, ALP-Haras, University of Berne, Länggasstrasse 124, Postfach 8466, Berne CH-3001, Switzerland. Electronic address: kathrin.maehlmann@vetsuisse.unibe.ch.
Hamza, E
  • Department of Clinical Research and Veterinary Public Health, University of Berne, Länggasstrasse 124, Postfach 8466, Berne CH-3001, Switzerland.
Marti, E
  • Department of Clinical Research and Veterinary Public Health, University of Berne, Länggasstrasse 124, Postfach 8466, Berne CH-3001, Switzerland.
Dolf, G
  • Institute of Genetics, University of Berne, Bremgartenstrasse 109a, Postfach 8466, Berne CH-3001, Switzerland.
Klukowska, J
  • Swiss Institute of Equine Medicine, ALP-Haras, University of Berne, Länggasstrasse 124, Postfach 8466, Berne CH-3001, Switzerland.
Gerber, V
  • Swiss Institute of Equine Medicine, ALP-Haras, University of Berne, Länggasstrasse 124, Postfach 8466, Berne CH-3001, Switzerland.
Koch, C
  • Swiss Institute of Equine Medicine, ALP-Haras, University of Berne, Länggasstrasse 124, Postfach 8466, Berne CH-3001, Switzerland.

MeSH Terms

  • Animals
  • Bovine papillomavirus 1 / physiology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Horse Diseases / genetics
  • Horse Diseases / immunology
  • Horses
  • Immunity, Innate
  • Male
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / veterinary
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / veterinary
  • Sarcoidosis / genetics
  • Sarcoidosis / immunology
  • Sarcoidosis / veterinary
  • Switzerland
  • T-Lymphocytes, Regulatory / immunology

Citations

This article has been cited 6 times.
  1. Hamza E, Cosandey J, Gerber V, Koch C, Unger L. The potential of three whole blood microRNAs to predict outcome and monitor treatment response in sarcoid-bearing equids. Vet Res Commun 2023 Jan;47(1):87-98.
    doi: 10.1007/s11259-022-09930-7pubmed: 35484337google scholar: lookup
  2. Unger L, Abril C, Gerber V, Jagannathan V, Koch C, Hamza E. Diagnostic potential of three serum microRNAs as biomarkers for equine sarcoid disease in horses and donkeys. J Vet Intern Med 2021 Jan;35(1):610-619.
    doi: 10.1111/jvim.16027pubmed: 33415768google scholar: lookup
  3. Crociati M, Capomaccio S, Mandara MT, Stradaioli G, Sylla L, Monaci M, Cappelli K. Different expression of Defensin-B gene in the endometrium of mares of different age during the breeding season. BMC Vet Res 2019 Dec 21;15(1):465.
    doi: 10.1186/s12917-019-2215-zpubmed: 31864349google scholar: lookup
  4. Wilson AD, Hicks C. Both tumour cells and infiltrating T-cells in equine sarcoids express FOXP3 associated with an immune-supressed cytokine microenvironment. Vet Res 2016 May 9;47(1):55.
    doi: 10.1186/s13567-016-0339-8pubmed: 27160146google scholar: lookup
  5. Vychodilova L, Plasil M, Futas J, Kopecka A, Molinkova D, Wijacki T, Jahn P, Knoll A, Horin P. Genetic susceptibility to sarcoid in Arabian horses: associations with MHC class II and compound MHC class I/KLRA genotypes. Vet Res Commun 2025 May 1;49(3):184.
    doi: 10.1007/s11259-025-10748-2pubmed: 40310488google scholar: lookup
  6. Beermann A, Clottu O, Reif M, Biegel U, Unger L, Koch C. A randomized placebo-controlled double-blinded study comparing oral and subcutaneous administration of mistletoe extract for the treatment of equine sarcoid disease. J Vet Intern Med 2024 May-Jun;38(3):1815-1824.
    doi: 10.1111/jvim.17052pubmed: 38529853google scholar: lookup