{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T05:42:01Z","timestamp":1793252521350,"version":"4.5.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T00:00:00Z","timestamp":1700438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Atopic dermatitis (AD) is one of the most common inflammatory skin diseases with complex pathogenesis involving epidermal barrier dysfunction, skin microbiome abnormalities and type-2-skewed immune dysregulation. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that plays critical roles in various biological processes. However, the role of STAT3 in epidermal keratinocytes in AD remains unclear. In this study, we generated an epidermal keratinocyte-specific <jats:italic>Stat3<\/jats:italic>-deficient mouse strain (termed <jats:italic>Stat3<\/jats:italic> cKO mice). After topical 2,4-dinitrochlorobenzene (DNCB) treatment, <jats:italic>Stat3<\/jats:italic> cKO mice developed worsened AD-like skin inflammation with increased Ki67<jats:sup>+<\/jats:sup> cells, decreased filaggrin and loricrin expression, and downregulated S100A9 and LL37. The dominant microbial population in <jats:italic>Stat3<\/jats:italic> cKO mice changed from <jats:italic>Ralstonia<\/jats:italic> to <jats:italic>Staphylococcus<\/jats:italic>. DNCB-treated <jats:italic>Stat3<\/jats:italic> cKO mice displayed more infiltrating type-2 inflammatory cells, including mast cells, eosinophils, and CD4<jats:sup>+<\/jats:sup>T cells, accompanied by increased skin IL-4 and serum IgE levels. Moreover, thymic stromal lymphopoietin (TSLP), mainly produced by keratinocytes, was highly expressed in the ear skin of <jats:italic>Stat3<\/jats:italic> cKO mice and chemoattracted more TSLPR<jats:sup>+<\/jats:sup> cells. TSLP blockade significantly alleviated DNCB-induced AD-like skin inflammation in <jats:italic>Stat3<\/jats:italic> cKO mice. Thus, epidermal keratinocyte-specific STAT3 deficiency can aggravate AD-like skin inflammation in mice, possibly through TSLP dysregulation.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1273182","type":"journal-article","created":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T05:00:26Z","timestamp":1700456426000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Epidermal keratinocyte-specific STAT3 deficiency aggravated atopic dermatitis-like skin inflammation in mice through TSLP upregulation"],"prefix":"10.3389","volume":"14","author":[{"given":"Zhao-Yuan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Xin","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Zhe","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Yan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Qi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing-Xi","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Yong","family":"Man","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00149-X","article-title":"Atopic 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