{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:44:54Z","timestamp":1790671494456,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T00:00:00Z","timestamp":1626825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006197","name":"Fonden til L\u00e6gevidenskabens Fremme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006197","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012331","name":"LEO Fondet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012331","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Allergic contact dermatitis (ACD) is classically described as a delayed\u2010type hypersensitivity reaction. However, patients often experience flare\u2010ups characterized by itching erythema, edema, and often vesicles occurring within hours after re\u2010exposure of previously sensitized skin to the specific contact allergen. Recent studies have indicated that skin\u2010resident memory T (T<jats:sub>RM<\/jats:sub>) cells play a central role in ACD. However, the pathogenic role of T<jats:sub>RM<\/jats:sub> cells in allergen\u2010induced flare\u2010ups is not known.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>By the use of various mouse models and cell depletion protocols, we investigated the role of epidermal T<jats:sub>RM<\/jats:sub> cells in flare\u2010up reactions to the experimental contact allergen 1\u2010fluoro\u20102,4\u2010dinitrobenzene. The inflammatory response was measured by changes in ear thickness, and the cellular composition in epidermis was determined by flow cytometry and confocal microscopy. Finally, adaptive transfer and inhibitors were used to determine the role of T<jats:sub>RM<\/jats:sub> cells, neutrophils, and CXCL1\/CXCL2 in the response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We show that CD8<jats:sup>+<\/jats:sup> T<jats:sub>RM<\/jats:sub> cells initiate massive infiltration of neutrophils in the epidermis within 12\u00a0h after re\u2010exposure to the contact allergen. Depletion of neutrophils before re\u2010exposure to the allergen abrogated the flare\u2010up reactions. Furthermore, we demonstrate that CD8<jats:sup>+<\/jats:sup> T<jats:sub>RM<\/jats:sub> cells mediate neutrophil recruitment by inducing CXCL1 and CXCL2 production in the skin, and that blockage of the C\u2010X\u2010C chemokine receptor type 1 and 2 inhibits flare\u2010up reactions and neutrophil infiltration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>As the first, we show that epidermal CD8<jats:sup>+<\/jats:sup> T<jats:sub>RM<\/jats:sub> cells cause ACD flare\u2010ups by rapid recruitment of neutrophils to the epidermis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.14986","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T08:49:44Z","timestamp":1624610984000},"page":"513-524","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["CD8<sup>+<\/sup> tissue\u2010resident memory T cells recruit neutrophils that are essential for flare\u2010ups in contact dermatitis"],"prefix":"10.1111","volume":"77","author":[{"given":"Anders B.","family":"Funch","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology Faculty of Health and Medical Sciences The LEO Foundation Skin Immunology Research Center University of Copenhagen  Copenhagen Denmark"},{"name":"Department of Dermatology and Allergy National Allergy Research Center Copenhagen University Hospital Gentofte  Hellerup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Mraz","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology Faculty of Health and Medical Sciences The LEO Foundation Skin Immunology Research Center University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Sofie \u00d8.","family":"Gadsb\u00f8ll","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology Faculty of Health and 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