Elucidating the role of interleukin-17F in cutaneous T-cell lymphoma
Research output: Contribution to journal › Journal article › Research › peer-review
Inappropriately regulated expression of 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 Jak and Stat3 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 co-express IL-17A and IL-17F leading to formation of IL-17A/F heterodimers. Clinically, we demonstrate that IL-17F mRNA expression is significantly increased in CTCL skin lesions when compared to 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 observe that the expression of the IL-17 receptor is significantly increased in CTCL skin lesions when compared to 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.
Original language | English |
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Journal | Blood (online) |
Volume | 122 |
Issue number | 6 |
Pages (from-to) | 943-950 |
Number of pages | 8 |
ISSN | 1528-0020 |
DOIs | |
Publication status | Published - 25 Jun 2013 |
ID: 46483103