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

2013; Elsevier BV; Volume: 122; Issue: 6 Linguagem: Inglês

10.1182/blood-2013-01-480889

1528-0020

Thorbjørn Krejsgaard, Ivan V. Litvinov, Yang Wang, Lixin Xia, Andreas Willerslev-Olsen, Sergei B. Koralov, Katharina Kopp, Charlotte M. Bonefeld, Mariusz A. Wasik, Carsten Geisler, Anders Woetmann, Youwen Zhou, Denis Sasseville, Niels Ødum,

Nail Diseases and Treatments

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.