Elucidating the role of interleukin-17F in cutaneous T-cell lymphoma.

Abstract

Inappropriately regulated expression of interleukin (IL)-17A is associated with the development of inflammatory diseases and cancer. However, little is known about the role of other IL-17 family members in carcinogenesis. Here, we show that a set of malignant T-cell lines established from patients with cutaneous T-cell lymphoma (CTCL) spontaneously secrete IL-17F and that inhibitors of Janus kinases and Signal transducer and activator of transcription 3 are able to block that secretion. Other malignant T-cell lines produce IL-17A but not IL-17F. Upon activation, however, some of the malignant T-cell lines are able to coexpress IL-17A and IL-17F, leading to formation of IL-17A/F heterodimers. Clinically, we demonstrate that IL-17F messenger RNA expression is significantly increased in CTCL skin lesions compared with healthy donors and patients with chronic dermatitis. IL-17A expression is also increased and a significant number of patients express high levels of both IL-17A and IL-17F. Concomitantly, we observed that the expression of the IL-17 receptor is significantly increased in CTCL skin lesions compared with control subjects. Importantly, analysis of a historic cohort of 60 CTCL patients indicates that IL-17F expression is associated with progressive disease. These findings implicate IL-17F in the pathogenesis of CTCL and suggest that IL-17 cytokines and their receptors may serve as therapeutic targets.

• Authors: Thorbjørn Krejsgaard, Ivan V Litvinov, Yang Wang, Lixin Xia, Andreas Willerslev-Olsen, Sergei B Koralov, Katharina L Kopp, Charlotte M Bonefeld, Mariusz A Wasik, Carsten Geisler, Anders Woetmann, Youwen Zhou, Denis Sasseville, Niels Odum
• Journal: Blood (Blood) Vol. 122 Issue 6 Pg. 943-50 (Aug 08 2013) ISSN: 1528-0020 [Electronic] United States
• PMID: 23801634 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Interleukin-17
• STAT3 Transcription Factor
• STAT3 protein, human
• Janus Kinases

Topics

• Biopsy
• Cell Line, Tumor
• Cytokines (metabolism)
• Disease Progression
• Female
• Gene Expression Regulation
• Gene Expression Regulation, Neoplastic
• Humans
• Interleukin-17 (metabolism)
• Janus Kinases (metabolism)
• Jurkat Cells
• Lymphoma, T-Cell, Cutaneous (metabolism)
• Male
• Mycosis Fungoides (metabolism)
• STAT3 Transcription Factor (metabolism)
• Skin (pathology)