Dataset Information

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

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.

SUBMITTER: Hu T

PROVIDER: S-EPMC6690676 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Hu Tengpeng T Buus Terkild Brink TB Krejsgaard Thorbjørn T Nansen Anneline A Lundholt Betina Kerstin BK Spee Pieter P Fredholm Simon S Petersen David Leander DL Blümel Edda E Gluud Maria M Monteiro Madalena N MN Willerslev-Olsen Andreas A Andersen Mads Hald MH Straten Per Thor PT Met Özcan Ö Met Özcan Ö Stolearenco Veronica V Fogh Hanne H Gniadecki Robert R Nastasi Claudia C Litman Thomas T Woetmann Anders A Gjerdrum Lise Mette Rahbek LMR Ødum Niels N

Oncotarget 20190806 47

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 i ...[more]

PMID: 31448055

Similar Datasets

Project description:BackgroundMicroarray hybridization studies in Sézary syndrome (SS) have compared T lymphocytes from patients with cutaneous T-cell lymphoma with those of normal controls; a major limitation of this design is that significant inherent genetic variability of lymphocyte populations between individuals may produce differences in gene expression unrelated to disease state.ObjectiveThe objective of this study was to minimize the heterogeneity of information derived from whole-genome expression analysis and to identify specific genetic differences between highly purified malignant and nonmalignant (control) T cells from the same patient with SS.MethodsPeripheral blood mononuclear cells were obtained from a patient with SS, stained with anti-T-cell receptor Vb (TCR-Vb) antibodies, and sorted by multiparameter flow cytometry. Malignant cells expressed the dominant TCR-Vb; control T cells lacked the dominant TCR-Vb but were otherwise phenotypically identical (CD3+CD4+CD45RO+). These cell populations were compared using the Illumina Inc. Sentrix Human-6 expression BeadChip system.ResultsTranscriptome analysis using the J5 test, which was selected for data analysis based on an efficiency analysis of competing statistical methods, showed differential expression of 44 genes between the malignant and nonmalignant cell subsets. Promyelocytic leukaemia zinc finger protein (ZBTB16) was the most profoundly upregulated gene in the malignant cell population, while interferon regulatory factor 3 (IRF3) and interferon-induced protein 35 (IFI35), which are important elements of the cellular response to viral infection, were significantly downregulated.ConclusionsThe results of this study suggest the feasibility of this novel comparative approach to genomic profiling in SS. Using this method, we identified several differentially expressed genes and pathways not previously described in SS. While these findings require validation in larger studies, they may be important in SS pathogenesis.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets