Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 45, Issue 9, Pages 2602-2614Publisher
WILEY
DOI: 10.1002/eji.201445208
Keywords
K(V)1.3; Membrane potential; NK cells; Potassium channels; TASK2
Categories
Funding
- German Research foundation (DFG) [BI1822/1-1, ME 3283/2-1, INST 2105/27-1, GR 3946/2-1]
- Interdisciplinary Centre for Clinical Research (IZKF) Munster [SEED 03/12]
- Innovative Medical Science [AL 12 11 08, I-BI111316]
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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 K(V)1.3 and the calcium-activated K(Ca)3.1 channels, human NK cells also express the two-pore domain K2P 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.
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