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Plasma membrane lipid scrambling causing Phosphatidylserine exposure negatively regulates NK cell activation

Cellular & Molecular Immunology 2021年第3期18卷 686-697页

作者： Ning Wu Hua Song Andre Veillette Laboratory of Molecular Oncology Institut de recherches cliniques de Montreal(IRCM)MontrealQC H2W1R7Canada Department of Immunology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and Technology(HUST)WuhanChina Department of Medicine University of MontrealMontrealQC H3C3J7Canada Department of Medicine McGill UniversityMontrealQC H3G 1Y6f Canada

One of the hallmarks of live cells is the asymmetric distribution of lipids across their plasma membrane.Changes in this asymmetry due to lipid"scrambling"result in Phosphatidylserine exposure at the cell surface that is detected by annexin V staining.This alteration is observed during cell death processes such as apoptosis,and during physiological responses such as platelet degranulation and membrane repair.Previous studies have shown that activation of NK cells is accompanied by exposure of phosphatidylserine at the cell surface.While this response was thought to be indicative of ongoing NK cell death,it may also reflect the regulation of NK cell activation in the absence of cell death.Herein,we found that NK cell activation was accompanied by rapid Phosphatidylserine exposure to an extent proportional to the degree of NK cell activation.Through enforced expression of a lipid scramblase,we provided evidence that activation-induced lipid scrambling in NK cells is reversible and does not lead to cell death.In contrast,lipid scrambling attenuates NKcell activation.This response was accompanied by reduced cell surface expression of activating receptors such as 2B4,and by loss of binding of Src family protein tyrosine kinases Fyn and Lck to the inner leaflet of the plasma membrane.Hence,lipid scrambling during NK cell activation is,at least in part,a physiological response that reduces the NK cell activation level.This effect is due to the ability of lipid scrambling to alter the distribution of membrane-associated receptors and kinases required for NK cell activation.

关键词： NK cell activation Phosphatidylserine exposure Lipid scrambling TMEM16F Signaling

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