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- Title
Malignant cutaneous T-cell lymphoma cells express IL-17 utilizing the Jak3/Stat3 signaling pathway.
- Authors
Krejsgaard, Thorbjørn; Ralfkiaer, Ulrik; Clasen-Linde, Erik; Eriksen, Karsten W; Kopp, Katharina L; Bonefeld, Charlotte M; Geisler, Carsten; Dabelsteen, Sally; Wasik, Mariusz A; Ralfkiaer, Elisabeth; Woetmann, Anders; Odum, Niels
- 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.
- Publication
The Journal of investigative dermatology, 2011, Vol 131, Issue 6, p1331
- ISSN
1523-1747
- Publication type
Journal Article
- DOI
10.1038/jid.2011.27