title: 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.
authors.affiliation: 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.
authors.forename: K
authors.initials: K
authors.lastname: Mählmann
authors.affiliation: Department of Clinical Research and Veterinary Public Health, University of Berne, Länggasstrasse 124, Postfach 8466, Berne CH-3001, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Hamza
authors.affiliation: Department of Clinical Research and Veterinary Public Health, University of Berne, Länggasstrasse 124, Postfach 8466, Berne CH-3001, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Marti
authors.affiliation: Institute of Genetics, University of Berne, Bremgartenstrasse 109a, Postfach 8466, Berne CH-3001, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Dolf
authors.affiliation: Swiss Institute of Equine Medicine, ALP-Haras, University of Berne, Länggasstrasse 124, Postfach 8466, Berne CH-3001, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Klukowska
authors.affiliation: Swiss Institute of Equine Medicine, ALP-Haras, University of Berne, Länggasstrasse 124, Postfach 8466, Berne CH-3001, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Gerber
authors.affiliation: Swiss Institute of Equine Medicine, ALP-Haras, University of Berne, Länggasstrasse 124, Postfach 8466, Berne CH-3001, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Koch
mesh_terms: D000818:Animals; D052688:Bovine papillomavirus 1 / Q000502:physiology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D006734:Horse Diseases / Q000235:genetics* / Q000276:immunology; D006736:Horses; D007113:Immunity, Innate; D008297:Male; D030361:Papillomavirus Infections / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D012507:Sarcoidosis / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D013557:Switzerland; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger
keywords: BPV; Equine sarcoid; FOXP3; Horse; Regulatory T cells