Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome
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- Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome
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The voltage-gated potassium channel Kv1.3 (KCNA3) is expressed by a subset of chronically activated memory T cells and plays an important role in their activation and proliferation. Here, we show that primary malignant T cells isolated from patients with Sézary syndrome (SS) express Kv1.3 and are sensitive to potent Kv1.3 inhibitors ShK and Vm24, but not sensitive to a less potent inhibitor [N17A/F32T]-AnTx. Kv1.3 blockade inhibits CD3/CD28-induced proliferation and IL-9 expression by SS cells in a concentration-dependent manner. In parallel, CD3/CD28-mediated CD25 induction is inhibited, whereas Kv1.3 blockade has no effect on apoptosis or cell death as judged by Annexin V and PI staining. In conclusion, we provide the first evidence that malignant T cells in SS express functional Kv1.3 channels and that Kv1.3 blockade inhibits activation-induced proliferation as well as cytokine and cytokine receptor expression in malignant T cells, suggesting that Kv1.3 is a potential target for therapy in SS.
Originalsprog | Engelsk |
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Tidsskrift | OncoTarget |
Vol/bind | 10 |
Udgave nummer | 47 |
Sider (fra-til) | 4894-4906 |
Antal sider | 13 |
ISSN | 1949-2553 |
DOI | |
Status | Udgivet - 2019 |
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