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In this work, we found decreased bacterial density and dysbiosis associated with reduced amounts of\n                    <jats:italic>Staphylococcus<\/jats:italic>\n                    in the skin of PPAR\u03b1-deficient mice compared to littermate controls. The NOD2 pathway was enhanced, as shown by up-regulation of both NOD2 and its downstream targets, including the antimicrobial peptides mBD3 and mBD4. Moreover, the Th17 immune response was enhanced in keratinocytes and epidermal dendritic T cells. Topical treatment of PPAR\u03b1-deficient mice with an antibacterial solution did not normalize the upregulation of the innate immunity in keratinocytes. However, the up-regulation of FLG and excessive oxidative stress detected in the epidermis of PPAR\u03b1-deficient mice were markedly inhibited by topical antibacterial treatment. Thus, our study highlights the overarching role of PPAR\u03b1 in shaping skin immune system and microbiota, with the latter largely controlling FLG expression and inducing oxidative stress in keratinocytes.\n                  <\/jats:p>","DOI":"10.1038\/s41419-026-08640-1","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T07:07:56Z","timestamp":1776150476000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["PPAR\u03b1 deficiency causes skin dysbiosis and triggers innate immunity in keratinocytes"],"prefix":"10.1038","volume":"17","author":[{"given":"Stefan","family":"Blunder","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Minzaghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Pavel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Berktold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Ploner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Sch\u00f6pf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florentine","family":"Marx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2936-8488","authenticated-orcid":false,"given":"Sandrine","family":"Dubrac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"8640_CR1","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.bbalip.2013.11.012","volume":"1841","author":"M Schmuth","year":"2014","unstructured":"Schmuth M, Moosbrugger-Martinz V, Blunder S, Dubrac S. 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