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

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 LitmanAnders Woetmann, Lise Mette Rahbek Gjerdrum, Niels Ødum

Publikation: Bidrag til tidsskriftArtikelForskningpeer review

Abstrakt

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.

OriginalsprogEngelsk
Sider (fra-til)4894-4906
Antal sider13
TidsskriftOncotarget
Vol/bind10
Udgave nummer47
DOI
StatusUdgivet - 6 aug. 2019

Fingeraftryk Udforsk hvilke forskningsemner 'Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome' indeholder.

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