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Panicot-Dubois, L.

Publications and source records attributed to Panicot-Dubois, L..

2 recordsLinked to original sources
bioRxiv2023

A thrombus is formed by a gradient of platelet activation and procoagulant endothelium

IntroductionThe contribution of platelets in thrombosis within microcirculation has been extensively documented in the literature. We previously showed, in vivo, that platelet activation revealed by intracellular calcium mobilization was a crucial step in the growth of thrombi following laser-induced injury, a model of thromboinflammation. AimWe employed a multimodal, correlative microscopy approach and computational biology to investigate the extent of platelet activation and the spatial distribution of platelets throughout a growing thrombus. ResultsWe observed a reversible intracellular platelet calcium mobilization that correlates with the time a platelet resides during thrombus growth. Our bioinformatics analysis displayed three distinct platelet subpopulations resident within a thrombus: (1) resting, (2) partially activated, and (3) "fully" activated platelets. The spatial distribution of the platelet subpopulations in the thrombus creates a double gradient in both the transversal and longitudinal axis, with the maximal percentage of fully activated platelets close to the site of injury. However, these activated platelets did not express negative phospholipids. The injured endothelium was identified to play a vital role in activating the blood coagulation cascade in this model of thrombosis. ConclusionFollowing a laser-induced injury, thrombi are formed by a gradient of activated platelets from the injury site to the periphery of the thrombus. These different activation states of platelets throughout the thrombi regulate the biomechanics of the thrombus. The injured endothelium, rather than platelets, was identified to play a key role in the activation of the blood coagulation cascade in this model of thromboinflammation. EssentialsO_LIComputational biology was used to analyze thrombosis. C_LIO_LINon-activated, low- and fully-activated platelets are part of a thrombus. C_LIO_LIThe activation of the platelets forms a gradient from the site of injury to the periphery. C_LIO_LIThe endothelium, and not platelets, expressed negative phospholipids. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=116 SRC="FIGDIR/small/550692v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@13ab958org.highwire.dtl.DTLVardef@5e7246org.highwire.dtl.DTLVardef@a07df6org.highwire.dtl.DTLVardef@adcbdb_HPS_FORMAT_FIGEXP M_FIG A thrombus is formed by a gradient of platelet activation and procoagulant endothelium C_FIG

physiology↗
bioRxiv2023

Targeting BTN2A1 enhances Vγ9Vδ2 T cell effector functions and triggers tumor cells pyroptosis

V{gamma}9V{delta}2 T cells are potent but elusive cytotoxic effectors. Means to stimulate their function could lead to powerful new cancer immunotherapies. BTN2A1, a surface protein has recently been shown to bind the V{gamma}9 chain of the {gamma}{delta} TCR but its precise role in modulating V{gamma}9V{delta}2 T cells functions remains unknown. Here we show that 107G3B5, a monoclonal anti-BTN2A1 agonist antibody, significantly enhances V{gamma}9V{delta}2 T cell functions against hematological or solid cell lines and against primary cells from adult acute lymphoblastic leukemia patients. New computer vision strategies applied to holotomographic microscopy videos show that 107G3B5 enhances the interaction between V{gamma}9V{delta}2 T cells and target cells in a quantitative and qualitative manner. In addition, we provide evidence that V{gamma}9V{delta}2 T cells activated by 107G3B5 induce caspase 3/7 activation in tumor cells, thereby triggering their death by pyroptosis. We thus demonstrate that targeting BTN2A1 with 107G3B5 enhances the V{gamma}9V{delta}2 T cell antitumor response by triggering the pyroptosis-induced immunogenic cell death.

cancer biology↗