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While neuronal Transient Receptor Potential Ankyrin 1 (TRPA1) has been implicated in ACD, the role of keratinocyte TRPA1 remains unclear. We investigated whether allergen binding to keratinocyte TRPA1 drives cytotoxicity, cytokine release and inflammatory amplification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      We combined\n                      <jats:italic>in vivo<\/jats:italic>\n                      oxazolone\u2010induced hypersensitivity in wild\u2010type and\n                      <jats:italic>Trpa1<\/jats:italic>\n                      knockout mice with pharmacological inhibition by HC\u2010030031,\n                      <jats:italic>in vitro<\/jats:italic>\n                      assays using TRPA1\u2010expressing Chinese hamster ovary (CHO) cells and primary keratinocytes, RNAscope localisation in human and murine skin, cytokine profiling and\n                      <jats:italic>in silico<\/jats:italic>\n                      docking analyses of allergen\u2010TRPA1 interactions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      TRPA1 deletion or antagonism markedly reduced oxazolone\u2010induced ear swelling, vascular responses and histopathology. Strong contact sensitisers (2,4\u2010dinitrochlorobenzene [DNCB], 2,4\u2010dinitrofluorobenzene [DNFB], oxazolone and formaldehyde) activated TRPA1, inducing Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx, cytotoxicity and IL\u20101\n                      <jats:italic>\u03b1<\/jats:italic>\n                      release, effects absent in\n                      <jats:italic>Trpa1<\/jats:italic>\n                      \u2010deficient cells and inhibited by HC\u2010030031. RNAscope confirmed keratinocyte TRPA1 expression in human and mouse skin. Docking revealed allergen\u2010specific binding modes, where covalent cysteine modification and A\u2010loop stabilisation correlated with potency. Consistent with these observations allergen\u2010induced ROS, which also target the cysteine cluster of TRPA1, may further lower the channel's activation threshold and thereby amplify allergen\u2010driven cytotoxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>\n                      Keratinocyte TRPA1 integrates direct allergen binding with ROS\u2010mediated sensitisation to drive cytotoxicity and IL\u20101\n                      <jats:italic>\u03b1<\/jats:italic>\n                      release. This dual mechanism helps explain sensitiser potency and positions TRPA1 antagonism as a promising therapeutic approach in ACD, while providing a framework for chemical risk assessment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70479","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T05:34:19Z","timestamp":1777613659000},"page":"4610-4627","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Contact sensitisers activate keratinocytes and induce cytotoxicity via Transient Receptor Potential Ankyrin 1 in allergic contact dermatitis"],"prefix":"10.1111","volume":"183","author":[{"given":"Areej","family":"Jaber","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School University of P\u00e9cs  P\u00e9cs Hungary"},{"name":"Department of Dermatology, Venereology, and Oncodermatology, Medical School University of P\u00e9cs  P\u00e9cs Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szabina","family":"Horv\u00e1th","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology, and Oncodermatology, Medical School University of P\u00e9cs  P\u00e9cs Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bal\u00e1zs Zolt\u00e1n","family":"Zsid\u00f3","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School University of P\u00e9cs  P\u00e9cs Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikt\u00f3ria","family":"Kormos","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School University of P\u00e9cs  P\u00e9cs Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e1nos","family":"Konkoly","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and 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