Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome
| Autor: | Thorbjørn Krejsgaard, Niels Ødum, Mads Hald Andersen, Veronica Stolearenco, Özcan Met, David L. Petersen, Pieter Spee, Terkild B. Buus, Andreas Willerslev-Olsen, Thomas Litman, Per thor Straten, Tengpeng Hu, Simon Fredholm, Lise Mette Rahbek Gjerdrum, Anders Woetmann, Edda Blümel, Anneline Nansen, Hanne Fogh, Maria Gluud, Robert Gniadecki, Betina Kerstin Lundholt, Claudia Nastasi, Madalena N Monteiro |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
CD3 medicine.medical_treatment Kv1.3 channel complex mixtures 03 medical and health sciences 0302 clinical medicine medicine cancer natural sciences IL-2 receptor cutaneous T-cell lymphoma biology Chemistry urogenital system Cutaneous T-cell lymphoma ShK medicine.disease KCNA3 Blockade 030104 developmental biology Cytokine Oncology nervous system Apoptosis 030220 oncology & carcinogenesis Sézary syndrome Cancer research biology.protein biological phenomena cell phenomena and immunity Cytokine receptor Research Paper |
| Zdroj: | Oncotarget Hu, T, Buus, T B, Krejsgaard, T, Nansen, A, Lundholt, B K, Spee, P, Fredholm, S, Petersen, D L, Blümel, E, Gluud, M, Monteiro, M N, Willerslev-Olsen, A, Andersen, M H, Straten, P T, Met, Ö, Stolearenco, V, Fogh, H, Gniadecki, R, Nastasi, C, Litman, T, Woetmann, A, Gjerdrum, L M R & Ødum, N 2019, ' Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome ', OncoTarget, vol. 10, no. 47, pp. 4894-4906 . https://doi.org/10.18632/oncotarget.27122 |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.27122 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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