title: Malignant cutaneous T-cell lymphoma cells express IL-17 utilizing the Jak3/Stat3 signaling pathway.
abstract: IL-17 is a proinflammatory cytokine that is crucial for the host's protection against a range of extracellular pathogens. However, inappropriately regulated expression of IL-17 is associated with the development of inflammatory diseases and cancer. In cutaneous T-cell lymphoma (CTCL), malignant T cells gradually accumulate in skin lesions characterized by massive chronic inflammation, suggesting that IL-17 could be involved in the pathogenesis. In this study we show that IL-17 protein is present in 10 of 13 examined skin lesions but not in sera from 28 CTCL patients. Importantly, IL-17 expression is primarily observed in atypical lymphocytes with characteristic neoplastic cell morphology. In accordance, malignant T-cell lines from CTCL patients produce IL-17 and the synthesis is selectively increased by IL-2 receptor β chain cytokines. Small-molecule inhibitors or small interfering RNA against Jak3 and signal transducer and activator of transcription 3 (Stat3) reduce the production of IL-17, showing that the Jak3/Stat3 pathway promotes the expression of the cytokine. In summary, our findings indicate that the malignant T cells in CTCL lesions express IL-17 and that this expression is promoted by the Jak3/Stat3 pathway.
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thorbjørn
authors.initials: T
authors.lastname: Krejsgaard
authors.forename: Ulrik
authors.initials: U
authors.lastname: Ralfkiaer
authors.forename: Erik
authors.initials: E
authors.lastname: Clasen-Linde
authors.forename: Karsten W
authors.initials: KW
authors.lastname: Eriksen
authors.forename: Katharina L
authors.initials: KL
authors.lastname: Kopp
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Bonefeld
authors.forename: Carsten
authors.initials: C
authors.lastname: Geisler
authors.forename: Sally
authors.initials: S
authors.lastname: Dabelsteen
authors.forename: Mariusz A
authors.initials: MA
authors.lastname: Wasik
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ralfkiaer
authors.forename: Anders
authors.initials: A
authors.lastname: Woetmann
authors.forename: Niels
authors.initials: N
authors.lastname: Odum
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D020381:Interleukin-17 / Q000032:analysis / Q000502:physiology*; D053616:Janus Kinase 3 / Q000502:physiology*; D016410:Lymphoma, T-Cell, Cutaneous / Q000209:etiology / Q000276:immunology*; D050796:STAT3 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D012878:Skin Neoplasms / Q000209:etiology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D020381:Interleukin-17; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C507933:JAK3 protein, human; D053616:Janus Kinase 3