{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T19:36:34Z","timestamp":1785526594620,"version":"3.56.0"},"reference-count":53,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"31","funder":[{"name":"National Institute of Health grant","award":["DK125407"],"award-info":[{"award-number":["DK125407"]}]},{"name":"National Institute of Health grant","award":["DK109677"],"award-info":[{"award-number":["DK109677"]}]},{"name":"National Institute of Health grant","award":["DK109677"],"award-info":[{"award-number":["DK109677"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,7,31]]},"abstract":"<jats:p>\n                    Neutrophil migration involves a dynamic balance of chemoattractant and inhibitory signals. We previously identified hepoxilin A\n                    <jats:sub>3<\/jats:sub>\n                    (HxA\n                    <jats:sub>3<\/jats:sub>\n                    ) as a potent chemoattractant that directs neutrophil migration across intestinal epithelia and showed that endocannabinoids can suppress migration through the cannabinoid 2 receptor (CB\n                    <jats:sub>2<\/jats:sub>\n                    R). Here, we reveal that HxA\n                    <jats:sub>3<\/jats:sub>\n                    uses the transient receptor potential vanilloid type 2 (TRPV2) cation channel to promote transmigration, a process finely tuned by physical TRPV2-CB\n                    <jats:sub>2<\/jats:sub>\n                    R interaction. In resting neutrophils, surface-localized CB\n                    <jats:sub>2<\/jats:sub>\n                    R responding to endocannabinoids suppresses migration, while a small fraction of TRPV2 at the plasma membrane \u201csenses\u201d HxA\n                    <jats:sub>3<\/jats:sub>\n                    . HxA\n                    <jats:sub>3<\/jats:sub>\n                    drives the movement of an intracellular \u201cstorage\u201d pool of TRPV2 to the leading edge of migration where physical interaction with CB\n                    <jats:sub>2<\/jats:sub>\n                    R establishes cell surface receptor complexes to direct neutrophil migration. Postactivation, TRPV2 is shunted toward degradation, while CB\n                    <jats:sub>2<\/jats:sub>\n                    R is both replaced and recycled to the plasma membrane to establish a coordinated system capable of maintaining directional fidelity to HxA\n                    <jats:sub>3<\/jats:sub>\n                    gradients. These findings uncover a previously unrecognized layer of neutrophil trafficking regulation.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adz1986","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T17:58:34Z","timestamp":1785520714000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Transient receptor potential vanilloid 2 functions as a directional driver for hepoxilin A\n                    <sub>3<\/sub>\n                    \u2013mediated neutrophil migration"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5184-5359","authenticated-orcid":true,"given":"Claudia","family":"Feriotti","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Center for Therapeutic Innovation, University of Bath, Claverton Down, Bath BA2 7AY, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regino","family":"Mercado-Lubo","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merran","family":"Bryford","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Center for Therapeutic Innovation, University of Bath, Claverton Down, Bath BA2 7AY, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9709-766X","authenticated-orcid":true,"given":"Rebecca","family":"Ferrisi","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia, Universit\u00e0 di Pisa, Via Bonanno 6, 56126 Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2971-0834","authenticated-orcid":true,"given":"Francesca","family":"Gado","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia, Universit\u00e0 di Pisa, Via Bonanno 6, 56126 Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7379-5743","authenticated-orcid":true,"given":"Clementina","family":"Manera","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia, Universit\u00e0 di Pisa, Via Bonanno 6, 56126 Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia, Universit\u00e0 di Pisa, Via Bonanno 6, 56126 Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4111-2023","authenticated-orcid":true,"given":"Yushuan","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth A.","family":"McCormick","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8505-8516","authenticated-orcid":true,"given":"Randall","family":"Mrsny","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Center for Therapeutic Innovation, University of Bath, Claverton Down, Bath BA2 7AY, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2019.05.001"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.061168"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00220"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2017.07.001"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400832101"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.11.8044"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI96817"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-021-01137-3"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-5846(99)00052-4"},{"key":"e_1_3_2_11_2","first-page":"291","article-title":"Coupling of hepoxilin A3-specific binding with calcium-mobilizing actions in human neutrophils","volume":"45","author":"Reynaud D.","year":"1995","unstructured":"D. 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