{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T09:10:59Z","timestamp":1784279459348,"version":"3.55.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:00:00Z","timestamp":1684454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012016","name":"Nipponham Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012016","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008731","name":"Nakatomi Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012359","name":"Promotion and Mutual Aid Corporation for Private Schools of Japan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with food allergy often suffer from atopic dermatitis, in which <jats:italic>Staphylococcus aureus<\/jats:italic> colonization is frequently observed. <jats:italic>Staphylococcus aureus<\/jats:italic> \u03b4-toxin activates mast cells and promotes T helper 2 type skin inflammation in the tape-stripped murine skin. However, the physiological effects of \u03b4-toxin present on the steady-state skin remain unknown. We aimed to investigate whether \u03b4-toxin present on the steady-state skin impacts the development of food allergy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>The non-tape-stripped skins of wild-type, <jats:italic>Kit<jats:sup>W-sh\/W-sh<\/jats:sup><\/jats:italic>, or ST2-deficient mice were treated with ovalbumin (OVA) with or without \u03b4-toxin before intragastric administration of OVA. The frequency of diarrhea, numbers of jejunum or skin mast cells, and serum levels of OVA-specific IgE were measured. Conventional dendritic cell 2 (cDC2) in skin and lymph nodes (LN) were analyzed. The cytokine levels in the skin tissues or culture supernatants of \u03b4-toxin-stimulated murine keratinocytes were measured. Anti-IL-1\u03b1 antibody-pretreated mice were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Stimulation with \u03b4-toxin induced the release of IL-1\u03b1, but not IL-33, in murine keratinocytes. Epicutaneous treatment with OVA and \u03b4-toxin induced the local production of IL-1\u03b1. This treatment induced the translocation of OVA-loaded cDC2 from skin to draining LN and OVA-specific IgE production, independently of mast cells and ST2. This resulted in OVA-administered food allergic responses. In these models, pretreatment with anti-IL-1\u03b1 antibody inhibited the cDC2 activation and OVA-specific IgE production, thereby dampening food allergic responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Even without tape stripping, \u03b4-toxin present on skin enhances epicutaneous sensitization to food allergen in an IL-1\u03b1-dependent manner, thereby promoting the development of food allergy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1173069","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T05:10:03Z","timestamp":1684473003000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Staphylococcus aureus \u03b4-toxin present on skin promotes the development of food allergy in a murine 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