Transient receptor potential vanilloid 2 functions as a directional driver for hepoxilin A₃-mediated neutrophil migration.

Authors

Claudia Feriotti, Regino Mercado-Lubo, Merran Bryford, Rebecca Ferrisi, Francesca Gado, Clementina Manera, Keyi Liu, Ping Lu, Yushuan Lai, Beth A McCormick, Randall Mrsny

Published in

Science advances. Volume 12. Issue 31. Pages eadz1986. Jul 31, 2026. Epub Jul 31, 2026.

Abstract

Neutrophil migration involves a dynamic balance of chemoattractant and inhibitory signals. We previously identified hepoxilin A₃ (HxA₃) as a potent chemoattractant that directs neutrophil migration across intestinal epithelia and showed that endocannabinoids can suppress migration through the cannabinoid 2 receptor (CB₂R). Here, we reveal that HxA₃ uses the transient receptor potential vanilloid type 2 (TRPV2) cation channel to promote transmigration, a process finely tuned by physical TRPV2-CB₂R interaction. In resting neutrophils, surface-localized CB₂R responding to endocannabinoids suppresses migration, while a small fraction of TRPV2 at the plasma membrane "senses" HxA₃. HxA₃ drives the movement of an intracellular "storage" pool of TRPV2 to the leading edge of migration where physical interaction with CB₂R establishes cell surface receptor complexes to direct neutrophil migration. Postactivation, TRPV2 is shunted toward degradation, while CB₂R is both replaced and recycled to the plasma membrane to establish a coordinated system capable of maintaining directional fidelity to HxA₃ gradients. These findings uncover a previously unrecognized layer of neutrophil trafficking regulation.

PMID:
42536751
Bibliographic data and abstract were imported from PubMed on 01 Aug 2026.

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