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Expression and function of Kv1.3 channel in malignant T cells in Sézary syndrome
- Source :
- 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 .
- Publication Year :
- 2019
-
Abstract
- 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.
Details
- Database :
- OAIster
- Journal :
- 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 .
- Notes :
- application/pdf, English
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1140009560
- Document Type :
- Electronic Resource