{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:43:55Z","timestamp":1793213035122,"version":"4.5.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T00:00:00Z","timestamp":1695168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016958","name":"Office of Research Infrastructure Programs, National Institutes of Health","doi-asserted-by":"publisher","award":["R21OD030057"],"award-info":[{"award-number":["R21OD030057"]}],"id":[{"id":"10.13039\/100016958","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC 2167, SFB 1526"],"award-info":[{"award-number":["EXC 2167, SFB 1526"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Inflammatory epidermolysis bullosa acquisita (EBA) is characterized by a neutrophilic response to anti-type VII collagen (COL7) antibodies resulting in the development of skin inflammation and blistering. The antibody transfer model of EBA closely mirrors this EBA phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To better understand the changes induced in neutrophils upon recruitment from peripheral blood into lesional skin in EBA, we performed single-cell RNA-sequencing of whole blood and skin dissociate to capture minimally perturbed neutrophils and characterize their transcriptome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Through this approach, we identified clear distinctions between circulating activated neutrophils and intradermal neutrophils. Most strikingly, the gene expression of multiple C-type lectin receptors, which have previously been reported to orchestrate host defense against fungi and select bacteria, were markedly dysregulated. After confirming the upregulation of <jats:italic>Clec4n<\/jats:italic>, <jats:italic>Clec4d<\/jats:italic>, and <jats:italic>Clec4e<\/jats:italic> in experimental EBA as well as in lesional skin from patients with inflammatory EBA, we performed functional studies in globally deficient <jats:italic>Clec4e<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> and <jats:italic>Clec4d<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice as well as in neutrophil-specific <jats:italic>Clec4n<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice. Deficiency in these genes did not reduce disease in the EBA model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Collectively, our results suggest that while the upregulation of <jats:italic>Clec4n<\/jats:italic>, <jats:italic>Clec4d<\/jats:italic>, and <jats:italic>Clec4e<\/jats:italic> is a hallmark of activated dermal neutrophil populations, their individual contribution to the pathogenesis of EBA is dispensable.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1266359","type":"journal-article","created":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T07:50:27Z","timestamp":1695282627000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["C-type lectin receptor expression is a hallmark of neutrophils infiltrating the skin in epidermolysis bullosa acquisita"],"prefix":"10.3389","volume":"14","author":[{"given":"Christian 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