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

Autor:	Hu T; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Buus TB; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Krejsgaard T; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Nansen A; Department of Molecular Pharmacology, Zealand Pharma A/S, Glostrup, Denmark., Lundholt BK; Department of Molecular Pharmacology, Zealand Pharma A/S, Glostrup, Denmark., Spee P; PS Pharmaconsult, Allerød, Denmark., Fredholm S; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Petersen DL; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Blümel E; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Gluud M; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Monteiro MN; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Willerslev-Olsen A; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Andersen MH; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.; Center for Cancer Immune Therapy, Department of Hematology, Copenhagen University Hospital at Herlev, Copenhagen, Denmark., Straten PT; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.; Center for Cancer Immune Therapy, Department of Hematology, Copenhagen University Hospital at Herlev, Copenhagen, Denmark., Met Ö; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.; Center for Cancer Immune Therapy, Department of Hematology, Copenhagen University Hospital at Herlev, Copenhagen, Denmark., Stolearenco V; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Fogh H; Department of Dermatology, Copenhagen University Hospital at Bispebjerg, Copenhagen, Denmark., Gniadecki R; Department of Dermatology, Copenhagen University Hospital at Bispebjerg, Copenhagen, Denmark., Nastasi C; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Litman T; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Woetmann A; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Gjerdrum LMR; Department of Pathology, Zealand University Hospital, Roskilde, Denmark., Ødum N; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2019 Aug 06; Vol. 10 (47), pp. 4894-4906. Date of Electronic Publication: 2019 Aug 06 (Print Publication: 2019).
DOI:	10.18632/oncotarget.27122
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. Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.
Databáze:	MEDLINE
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