Reinforcement of Integrin-Mediated T-Lymphocyte Adhesion by TNF

The mammalian inflammatory response significantly relies on integrin-mediated T-lymphocyte adhesion to endothelial cells. Whereas the outside-in signalling pathway of integrins in response to the proinflammatory cytokine tumor necrosis factor (TNF) has already been studied in detail, little knowledge exists about the inside-out signalling pathway of integrins in lymphocyte activation by TNF. We here show single-cell force spectroscopy (SCFS) data of T-lymphocyte (Jurkat E6-1) adhesion to fibronectin. Fibronectin is present on top of endothelial cell layers and is therefore a crucial player in mediating T-lymphocyte binding to endothelial cells. Our results show that activating integrins with TNF significantly increases the maximum adhesion force and detachment energy in Jurkat cell adhesion to fibronectin-coated surfaces. Analysis of single-molecule ruptures further proves that TNF reinforces integrin binding strength, particularly at sub-second timescales. Hence, our results provide quantitative evidence for the significant impact of TNF-induced inside-out signalling in the T-lymphocyte adhesion machinery.