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Veterinary research2016; 47(1); 55; doi: 10.1186/s13567-016-0339-8

Both tumour cells and infiltrating T-cells in equine sarcoids express FOXP3 associated with an immune-supressed cytokine microenvironment.

Abstract: Bovine papillomavirus (BPV) infections of equine species have a central role in the aetiology of equine sarcoids; a common benign skin tumour of horses, zebras and donkeys. Within the lesions, all of the early papillomavirus genes are expressed and promote the excessive replication of fibroblasts which characterise these tumours. Equine sarcoids differ from BPV induced fibro-papillomas of cattle (the natural host of BPV), in that they do not produce high amounts of virus particles, do not usually regress spontaneously and do not sero-convert to BPV; features which suggest that affected horses lack an effective anti-viral immune response to BPV. Equine sarcoids contain large numbers of CD4+ CD8+ dual positive T-cells which uniformly express FOXP3, the key transcription factor of regulatory T-cells, and FOXP3 is also expressed within the BPV infected fibroblasts. Compared to healthy skin, sarcoids showed increased mRNA transcription for FOXP3 and the regulatory cytokine TGFβ. Transcription of IL17, which has been shown to have a regulatory function in human papillomavirus-associated tumours, was also elevated in equine sarcoids compared to spleen. In contrast, the levels of mRNA transcripts for effector T cell cytokines IL2, IL4 and interferon-gamma (IFNγ) were not elevated in sarcoids compared to healthy skin or spleen. Similarly neither interferon-alpha (IFNα), interferon-beta (IFNβ) nor IL12 family members were elevated in sarcoids compared to normal skin. We suggest that the regulatory cytokine micro-environment within sarcoids enables the persistence of the lesions by preventing an effective anti-viral immune response.
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Publication Date: 2016-05-09 PubMed ID: 27160146PubMed Central: PMC4862206DOI: 10.1186/s13567-016-0339-8Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research explored the behavior of tumour cells and T-cells in equine sarcoids, a common skin tumor in horses, associated with Bovine papillomavirus infections. Specifically, the large presence of a key immune regulator, FOXP3, and certain cytokines suggest an immune-suppressed environment within these tumors that prevents an effective anti-viral response.

Understanding Equine Sarcoids and FOXP3

  • The study focusses on equine sarcoids, benign skin tumors commonly seen in horses, donkeys, and zebras. These sarcoids are linked to Bovine papillomavirus (BPV) infections.
  • The research highlights that all early papillomavirus gene expressions within the sarcoids promote excessive fibroblasts replication, a common characteristic of these tumors.
  • Unlike BPV-induced fibro-papillomas in cattle, equine sarcoids do not produce virus particles and generally do not regress or convert to BPV – indicating an ineffective anti-viral immune response.
  • The highlight of the study is the uniform expression of FOXP3, a key transcription factor of regulatory T-cells, found in both the T-cells and BPV infected fibroblasts within the sarcoids.
  • FOXP3, associated with immune suppression, might be playing a critical role in the persistence of these equine sarcoids.

Cytokine Microenvironment Inside The Sarcoids

  • Upon comparing sarcoids and healthy skin, the former showed an increased mRNA transcription for both FOXP3 and regulatory cytokine, TGFβ, indicating an immune-suppressed environment.
  • Elevated transcription of IL17, associated with regulatory functions in human papillomavirus-related tumors, was also found in equine sarcoids.
  • Contrary to the elevation in regulatory elements, no heightened mRNA transcripts levels for effector T cell cytokines – IL2, IL4, and interferon-gamma (IFNγ) were found. These elements usually promote immunity.
  • The study mentioned the absence of elevated mRNA transcripts levels for interferon-alpha (IFNα), interferon-beta (IFNβ), and IL12 family elements in sarcoids, compared to healthy skin.
  • The research suggests that the micro-environment within sarcoids, high in regulatory cytokines, might be preventing an effective anti-viral immune response, thereby promoting the persistence of equine sarcoids.

Cite This Article

APA
Wilson AD, Hicks C. (2016). Both tumour cells and infiltrating T-cells in equine sarcoids express FOXP3 associated with an immune-supressed cytokine microenvironment. Vet Res, 47(1), 55. https://doi.org/10.1186/s13567-016-0339-8

Publication

Veterinary research
ISSN: 1297-9716
NlmUniqueID: 9309551
Country: England
Language: English
Volume: 47
Issue: 1
Pages: 55
PII: 55

Researcher Affiliations

Wilson, A Douglas
  • School of Veterinary Sciences, University of Bristol, Langford, Bristol, BS40 5DU, UK. doug.wilson@bris.ac.uk.
Hicks, Chelsea
  • School of Veterinary Sciences, University of Bristol, Langford, Bristol, BS40 5DU, UK.

MeSH Terms

  • Animals
  • Cytokines / metabolism
  • Cytokines / physiology
  • Forkhead Transcription Factors / metabolism
  • Horse Diseases / immunology
  • Horse Diseases / metabolism
  • Horse Diseases / virology
  • Horses
  • Papillomaviridae
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / veterinary
  • Papillomavirus Infections / virology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin Neoplasms / immunology
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / veterinary
  • Skin Neoplasms / virology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / physiology
  • Tumor Microenvironment / immunology

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