Exploring The Role Of Piezo1 Mechanosensor In Human Monocyte Derived Dendritic Cell Migration

Abstract

Dendritic cells (DC) act as the sentinels of the immune system, which survey the blood and tissue for any foreign antigen and, upon antigen recognition, activate and modulate the behaviour of the adaptive immune system. Due to their function, migration becomes a crucial aspect of DC biology and is dependent on biochemical signals and specific adhesion molecules. Mechanical stimuli influence DC migration; however, the molecular mechanism behind mechanosensation in DC migration is not well understood. Piezo1, a recently discovered mechanosensitive calcium ion channel, needs only mechanical stimuli for its activation. It is shown to be well expressed in mammals, including the cells of the human immune system, making Piezo1 an excellent candidate for the mechanosensory ion channel in DC migration. We used GsMTx4, a peptide inhibitor of Piezo1, to explore its role in the migration of human monocyte-derived dendritic cells (MoDCs), which are in-vitro generated DC. We report that Piezo1 inhibition does not affect the motility of mature and immature MoDCs. Furthermore, Piezo1 expression gets downregulated upon MoDC maturation. However, Piezo1 inhibition reduces the 3D chemokine-induced directional migration of immature MoDCs. Our study suggests that Piezo1 directly influences the directed migration in immature MoDC, but MoDCs migrate in a Piezo1-independent manner upon maturation.