Regulace hladiny intracelulárního vápníku jako nástroj kontroly cytotoxicity NK buněk.

Graman, Vojtěch

NK cells, a subset of innate lymphoid cells, play a crucial role in recognizing and eliminating virally infected or cancerous cells, making them a promising cell-based immunotherapy for AML patients. However, NK cell-based immunotherapies face unforeseen efficacy problems. Intracellular Ca2+ signalling was shown to play a crucial part in NK cell cytotoxicity. Maintaining the intricate balance of intracellular Ca2+ signalling is vital for NK cell-mediated target cell killing. In the complex microenvironment of the patient's body, NK cells encounter various stimuli, which can potentially disrupt the balance of intracellular Ca2+ signalling. Stimulation of PRRs was shown to affect intracellular Ca2+ , further influencing overall NK cell cytotoxicity. This study investigated the impact of TLR stimulation on Ca2+ signalling and NK cell functions. The effect of TLR stimulation was assessed using Ca2+ influx measurement, functional cytotoxicity, and degranulation assay, as well as gene expression analysis. Exposure to TLR ligands resulted in elevation of intracellular Ca2+ levels, accompanied by a reduction of cytotoxic activity at low effector-to-target ratios. An increasing trend in degranulation was observed. Furthermore, gene expression analysis unveiled upregulation of NFAT and Orai1 in NK cells...

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