title: The two-pore domain K2 P channel TASK2 drives human NK-cell proliferation and cytolytic function.
abstract: Natural killer (NK) cells are a subset of cytotoxic lymphocytes that recognize and kill tumor- and virus-infected cells without prior stimulation. Killing of target cells is a multistep process including adhesion to target cells, formation of an immunological synapse, and polarization and release of cytolytic granules. The role of distinct potassium channels in this orchestrated process is still poorly understood. The current study reveals that in addition to the voltage-gated KV 1.3 and the calcium-activated KCa 3.1 channels, human NK cells also express the two-pore domain K2 P channel TASK2 (TWIK-related acid-sensitive potassium channel). Expression of Task2 varies among NK-cell subsets and depends on their differentiation and activation state. Despite its different expression in TASK2(high) CD56(bright) CD16(-) and TASK2(low) CD56(dim) CD16(+) NK cells, TASK2 is involved in cytokine-induced proliferation and cytolytic function of both subsets. TASK2 is crucial for leukocyte functional antigen (LFA-1) mediated adhesion of both resting and cytokine-activated NK cells to target cells, an early step in killing of target cells. With regard to the following mechanism, TASK2 plays a role in release of cytotoxic granules by resting, but not IL-15-induced NK cells. Taken together, our data exhibit two-pore potassium channels as important players in NK-cell activation and effector function.
authors.affiliation: Department of Neurology, University Hospital Münster, Münster, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schulte-Mecklenbeck
authors.affiliation: Department of Neurology, University Hospital Münster, Münster, Germany.|Interdisciplinary Centre for Clinical Research (IZKF), Münster, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bittner
authors.affiliation: Department of Neurology, University Hospital Münster, Münster, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Ehling
authors.affiliation: Institute of Physiology, University Würzburg, Würzburg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Döring
authors.affiliation: Institute of Physiology, University Würzburg, Würzburg, Germany.
authors.forename: Erhard
authors.initials: E
authors.lastname: Wischmeyer
authors.affiliation: Department of Neurology, University Hospital Münster, Münster, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Breuer
authors.affiliation: Department of Neurology, University Hospital Münster, Münster, Germany.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Herrmann
authors.affiliation: Department of Neurology, University Hospital Münster, Münster, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.affiliation: Department of Neurology, University Hospital Münster, Münster, Germany.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.affiliation: Department of Neurology, University Hospital Münster, Münster, Germany.
authors.forename: Catharina C
authors.initials: CC
authors.lastname: Gross
mesh_terms: D019002:CD56 Antigen / Q000235:genetics / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D054992:Immunological Synapses / Q000378:metabolism*; D019409:Interleukin-15 / Q000494:pharmacology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D061251:Primary Cell Culture; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D059010:Single-Cell Analysis
chemical_list: D019002:CD56 Antigen; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; C569274:IL15 protein, human; D019409:Interleukin-15; C410295:KCNK5 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; C522918:NCAM1 protein, human; D024683:Potassium Channels, Tandem Pore Domain; D017452:Receptors, IgG
keywords: KV1.3; Membrane potential; NK cells; Potassium channels; TASK2