期刊
BLOOD
卷 122, 期 6, 页码 943-950出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2013-01-480889
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资金
- Carlsberg Foundation
- Danish Cancer Society
- Dansk Kraeftforsknings Fond
- Danish Research Councils
- Danish National Advanced Technology Foundation
- Copenhagen Cluster of Immunology
- Lundbeck Foundation
- Novo Nordic Foundation
- Beckett Foundation (Beckett-Fonden)
- University of Copenhagen
- National Cancer Institute [CA89194]
- Canadian Dermatology Foundation
- Fonds de recherche du Quebec-Sante
- Novo Nordisk Fonden [NNF12OC0002036] Funding Source: researchfish
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.
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