Elucidating the role of interleukin-17F in cutaneous T-cell lymphoma
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Elucidating the role of interleukin-17F in cutaneous T-cell lymphoma. / 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.
In: Blood (online), Vol. 122, No. 6, 25.06.2013, p. 943-950.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Elucidating the role of interleukin-17F in cutaneous T-cell lymphoma
AU - Krejsgaard, Thorbjørn
AU - Litvinov, Ivan V
AU - Wang, Yang
AU - Xia, Lixin
AU - Willerslev-Olsen, Andreas
AU - Koralov, Sergei B
AU - Kopp, Katharina L
AU - Bonefeld, Charlotte M
AU - Wasik, Mariusz A
AU - Geisler, Carsten
AU - Woetmann, Anders
AU - Zhou, Youwen
AU - Sasseville, Denis
AU - Odum, Niels
PY - 2013/6/25
Y1 - 2013/6/25
N2 - 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.
AB - 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.
U2 - 10.1182/blood-2013-01-480889
DO - 10.1182/blood-2013-01-480889
M3 - Journal article
C2 - 23801634
VL - 122
SP - 943
EP - 950
JO - Blood
JF - Blood
SN - 0006-4971
IS - 6
ER -
ID: 46483103