Malignant cutaneous T-cell lymphoma cells express IL-17 utilizing the Jak3/Stat3 signaling pathway
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Malignant cutaneous T-cell lymphoma cells express IL-17 utilizing the Jak3/Stat3 signaling pathway. / Krejsgaard, Thorbjørn Frej; Ralfkiær, Ulrik; Clasen-Linde, Erik; Eriksen, Karsten Wessel Kam; Kopp, Katharina Luise Maria; Bonefeld, Charlotte Menne; Geisler, Carsten; Dabelsteen, Sally; Wasik, Mariusz A.; Ralfkiaer, Elisabeth Methner; Andersen, Anders Woetmann; Ødum, Niels.
In: Journal of Investigative Dermatology, Vol. 131, No. 6, 2011, p. 1331-1338.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Malignant cutaneous T-cell lymphoma cells express IL-17 utilizing the Jak3/Stat3 signaling pathway
AU - Krejsgaard, Thorbjørn Frej
AU - Ralfkiær, Ulrik
AU - Clasen-Linde, Erik
AU - Eriksen, Karsten Wessel Kam
AU - Kopp, Katharina Luise Maria
AU - Bonefeld, Charlotte Menne
AU - Geisler, Carsten
AU - Dabelsteen, Sally
AU - Wasik, Mariusz A.
AU - Ralfkiaer, Elisabeth Methner
AU - Andersen, Anders Woetmann
AU - Ødum, Niels
PY - 2011
Y1 - 2011
N2 - 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 ß 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.
AB - 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 ß 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.
U2 - 10.1038/jid.2011.27
DO - 10.1038/jid.2011.27
M3 - Journal article
C2 - 21346774
VL - 131
SP - 1331
EP - 1338
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 6
ER -
ID: 33732689