Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome. / Hu, Tengpeng; Buus, Terkild Brink; Krejsgaard, Thorbjørn; Nansen, Anneline; Lundholt, Betina Kerstin; Spee, Pieter; Fredholm, Simon; Petersen, David Leander; Blümel, Edda; Gluud, Maria; Monteiro, Madalena N; Willerslev-Olsen, Andreas; Andersen, Mads Hald; Straten, Per Thor; Met, Özcan; Stolearenco, Veronica; Fogh, Hanne; Gniadecki, Robert; Nastasi, Claudia; Litman, Thomas; Woetmann, Anders; Gjerdrum, Lise Mette Rahbek; Ødum, Niels.
In: OncoTarget, Vol. 10, No. 47, 2019, p. 4894-4906.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome
AU - Hu, Tengpeng
AU - Buus, Terkild Brink
AU - Krejsgaard, Thorbjørn
AU - Nansen, Anneline
AU - Lundholt, Betina Kerstin
AU - Spee, Pieter
AU - Fredholm, Simon
AU - Petersen, David Leander
AU - Blümel, Edda
AU - Gluud, Maria
AU - Monteiro, Madalena N
AU - Willerslev-Olsen, Andreas
AU - Andersen, Mads Hald
AU - Straten, Per Thor
AU - Met, Özcan
AU - Stolearenco, Veronica
AU - Fogh, Hanne
AU - Gniadecki, Robert
AU - Nastasi, Claudia
AU - Litman, Thomas
AU - Woetmann, Anders
AU - Gjerdrum, Lise Mette Rahbek
AU - Ødum, Niels
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
U2 - 10.18632/oncotarget.27122
DO - 10.18632/oncotarget.27122
M3 - Journal article
C2 - 31448055
VL - 10
SP - 4894
EP - 4906
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 47
ER -
ID: 226262605