Malignant cutaneous T-cell lymphoma cells express IL-17 utilizing the Jak3/Stat3 signaling pathway

Thorbjørn Frej Krejsgaard; Ulrik Ralfkiær; Erik Clasen-Linde; Karsten Wessel Kam Eriksen; Katharina Luise Maria Kopp; Charlotte Menne Bonefeld; Carsten Geisler; Sally Dabelsteen; Mariusz A. Wasik; Elisabeth Methner Ralfkiaer; Anders Woetmann Andersen; Niels Ødum

doi:10.1038/jid.2011.27

Malignant cutaneous T-cell lymphoma cells express IL-17 utilizing the Jak3/Stat3 signaling pathway

Thorbjørn Frej Krejsgaard, Ulrik Ralfkiær, Erik Clasen-Linde, Karsten Wessel Kam Eriksen, Katharina Luise Maria Kopp, Charlotte Menne Bonefeld, Carsten Geisler, Sally Dabelsteen, Mariusz A. Wasik, Elisabeth Methner Ralfkiaer, Anders Woetmann Andersen, Niels Ødum

83 Citations (Scopus)

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.

Original language	English
Journal	Journal of Investigative Dermatology
Volume	131
Issue number	6
Pages (from-to)	1331-1338
Number of pages	8
ISSN	0022-202X
DOIs	https://doi.org/10.1038/jid.2011.27
Publication status	Published - Jun 2011

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Krejsgaard, T. F., Ralfkiær, U., Clasen-Linde, E., Eriksen, K. W. K., Kopp, K. L. M., Bonefeld, C. M., Geisler, C., Dabelsteen, S., Wasik, M. A., Ralfkiaer, E. M., Andersen, A. W., & Ødum, N. (2011). Malignant cutaneous T-cell lymphoma cells express IL-17 utilizing the Jak3/Stat3 signaling pathway. Journal of Investigative Dermatology, 131(6), 1331-1338. https://doi.org/10.1038/jid.2011.27

Krejsgaard, TF, Ralfkiær, U, Clasen-Linde, E, Eriksen, KWK, Kopp, KLM, Bonefeld, CM, Geisler, C , Dabelsteen, S, Wasik, MA, Ralfkiaer, EM, Andersen, AW & Ødum, N 2011, 'Malignant cutaneous T-cell lymphoma cells express IL-17 utilizing the Jak3/Stat3 signaling pathway', Journal of Investigative Dermatology, vol. 131, no. 6, pp. 1331-1338. https://doi.org/10.1038/jid.2011.27

@article{4922ccf29260404fbee5e13832f02446,

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.",

author = "Krejsgaard, {Thorbj{\o}rn Frej} and Ulrik Ralfki{\ae}r and Erik Clasen-Linde and Eriksen, {Karsten Wessel Kam} and Kopp, {Katharina Luise Maria} and Bonefeld, {Charlotte Menne} and Carsten Geisler and Sally Dabelsteen and Wasik, {Mariusz A.} and Ralfkiaer, {Elisabeth Methner} and Andersen, {Anders Woetmann} and Niels {\O}dum",

year = "2011",

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doi = "10.1038/jid.2011.27",

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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 - 2011/6

Y1 - 2011/6

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 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.

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 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.

U2 - 10.1038/jid.2011.27

DO - 10.1038/jid.2011.27

M3 - Journal article

C2 - 21346774

SN - 0022-202X

VL - 131

SP - 1331

EP - 1338

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

IS - 6

ER -

Malignant cutaneous T-cell lymphoma cells express IL-17 utilizing the Jak3/Stat3 signaling pathway

Abstract

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