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

• Published in: Blood Vol. 122; no. 6; pp. 943 - 950
• Main Authors: Krejsgaard, Thorbjørn, Litvinov, Ivan V., Wang, Yang, Xia, Lixin, Willerslev-Olsen, Andreas, Koralov, Sergei B., Kopp, Katharina L., Bonefeld, Charlotte M., Wasik, Mariusz A., Geisler, Carsten, Woetmann, Anders, Zhou, Youwen, Sasseville, Denis, Odum, Niels
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.08.2013; American Society of Hematology
• Subjects: 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; Lymphoid Neoplasia; Lymphoma, T-Cell, Cutaneous - metabolism; Male; Mycosis Fungoides - metabolism; Skin - pathology; STAT3 Transcription Factor - metabolism
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2013-01-480889

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. •The Jak/Stat3 pathway promotes the expression of IL-17F in malignant CTCL cells.•IL-17F is highly expressed in a subset of CTCL patients and associated with progressive disease.