Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome

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Tengpeng Hu, Terkild Brink Buus, Thorbjørn Krejsgaard, Anneline Nansen, Betina Kerstin Lundholt, Pieter Spee, Simon Fredholm, David Leander Petersen, Edda Blümel, Maria Gluud, Madalena N Monteiro, Andreas Willerslev-Olsen, Mads Hald Andersen, Per Thor Straten, Özcan Met, Veronica Stolearenco, Hanne Fogh, Robert Gniadecki, Claudia Nastasi, Thomas Litman & 3 more Anders Woetmann, Lise Mette Rahbek Gjerdrum, Niels Ødum

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.

Original languageEnglish
JournalOncoTarget
Volume10
Issue number47
Pages (from-to)4894-4906
Number of pages13
ISSN1949-2553
DOIs
Publication statusPublished - 6 Aug 2019

ID: 226262605