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The immunocellular expression of Piezo1 thus makes it a strong candidate for mechanosensing at the plasma membrane to regulate motility of immune cells.

We previously identified crucial role of this specialized mechanotransducer in optimal TCR triggering ( 14, 19). Mechanosensing by Piezo1 has been demonstrated to play critical role in diverse patho-physiologic contexts given its wide tissue expression including the immunocellular compartment ( 13– 21).

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Piezo1 and Piezo2 ion channels are evolutionarily conserved professional mechanosensors that can sense increase in membrane tension mostly independent of other protein-protein interactions ( 10– 12). Mechanosensing of the substrate and increase in cellular membrane tension is also intuitively apparent in a migrating T cell, although mechanistic details are not explored to a great extent. Generation of mechanical force is critical to propel migrating cells ( 6– 9). The process is dependent on chemotactic cues, interaction between endothelial adhesion molecules and T cell integrins, and an intricate acto-myosin dynamics ( 5).

Thus we find that Piezo1 activation in response to local mechanical cues constitutes a membrane-intrinsic component of the ‘outside-in’ signaling in human T cells, migrating in response to chemokines, that mediates integrin recruitment to the leading edge.Įfficient T cell migration from blood circulation to secondary lymphoid organs and inflamed tissue is paramount for optimal tissue antigen sampling and effector functions during adaptive immune response ( 1– 4). Piezo1 recruitment and activation, followed by calcium influx and calpain activation, in turn are crucial for the integrin LFA-1 recruitment at the leading edge of the chemotactic human T cells. Piezo1 recruitment at the leading edge of moving T cells is dependent on and follows focal adhesion formation at the leading edge and local increase in membrane tension on chemokine receptor activation. We found that deficiency of Piezo1 in human T cells interfered with integrin-dependent cellular motility on ICAM-1-coated surface. We explored if the professional mechanosensor Piezo1 play any role during integrin-dependent chemotaxis of human T cells. A migrating T cell is expected to sense diverse external and membrane-intrinsic mechano-physical cues, but molecular mechanisms of such mechanosensing in cell migration are not established.

T cell extravasation in inflamed tissues depends on chemotactic cues and interaction between endothelial adhesion molecules and cellular integrins. T cells are crucial for efficient antigen-specific immune responses and thus their migration within the body, to inflamed tissues from circulating blood or to secondary lymphoid organs, play a very critical role.