Dataset for "Transient Receptor Potential Vanilloid 2 Functions as a Directional Driver for Hepoxilin A3-Mediated Neutrophil Migration"

Neutrophil migration involves a dynamic balance of chemoattractant and inhibitory signals. Mechanisms controlling their movement across mucosal barriers—such as the transition from the lamina propria into the intestinal lumen—have remained unresolved. We previously identified hepoxilin A3 (HxA3) as a potent chemoattractant that directs neutrophil migration across intestinal epithelia and showed that endocannabinoids can suppress this process through the CB2 receptor (CB2R). Here, we reveal that HxA3 uses the transient receptor potential vanilloid type 2 (TRPV2) cation channel to promote neutrophil transmigration, a process finely tuned by its direct physical interaction with CB2R. These findings uncover a previously unrecognized layer of regulation in neutrophil trafficking. In resting neutrophils, surface localized CB2R responds to endocannabinoids to suppress neutrophil migration, with a small fraction of TRPV2 stationed at the plasma membrane surface functioning to “sense” HxA3. An HxA3 gradient drives the movement of an intracellular “storage” pool of TRPV2 to the migration leading edge where physical interaction with CB2R establishes cell-surface receptor complexes to direct cell migration. Post-activation, TRPV2 is shunted to degradation pathways while CB2R is both replaced and recycled to the plasma membrane to establish a coordinated receptor organization and recycling system capable of maintaining directional fidelity to HxA3 gradients. This demonstration of coordinated functions of TRPV2-CB2R complexes at the cell surface capable of responding to both HxA3 and endocannabinoids redefines our understanding of directed neutrophil migration within mucosal tissues via a previously unappreciated signaling system involving a transient receptor potential channel and a G-protein coupled receptor.