{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T22:23:38Z","timestamp":1787783018445,"version":"build-2784847793"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Infection and Immunity Boost"},{"name":"Dutch Health Council"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Atopic dermatitis (AD) is characterized by dysregulated T cell immunity and skin microbiome dysbiosis with predominance of Staphylococcus aureus, which is associated with exacerbating AD skin inflammation. Specific glycosylation patterns of S. aureus cell wall structures amplify skin inflammation through interaction with Langerhans cells (LCs). Nevertheless, the role of LCs in AD remains poorly characterized. Here, we performed single cell RNA sequencing of primary epidermal LCs and dermal T cells, isolated from skin biopsies of AD patients and healthy control subjects, alongside specific glycoanalysis of S. aureus strains isolated from the AD lesions. Our findings revealed 4 LC subpopulations ie, 2 steady-state clusters [LC1 and LC1H] and 2 proinflammatory\/matured subsets [LC2 and migratory LCs]. The latter 2 subsets were enriched in AD skin. AD LCs showed enhanced expression of C-type lectin receptors, the high-affinity IgE receptor, and activation of prostaglandin and leukotriene biosynthesis pathways, upregulated transcriptional signatures related to T cell activation pathways, and increased expression of CCL17 compared with healthy LCs. Correspondingly, T helper 2 and T regulatory cell populations were increased in AD lesions. Complementary, we performed bulk RNA sequencing of primary LCs stimulated with the S. aureus strains isolated from the AD lesions, which showed upregulation of T helper 2\u2013related pathways. Our study provides proof-of-concept for a role of LCs in connecting the S. aureus\u2013T cell axis in the AD inflammatory cycle.<\/jats:p>","DOI":"10.1093\/immhor\/vlae009","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T04:00:51Z","timestamp":1737691251000},"source":"Crossref","is-referenced-by-count":8,"title":["Single-cell sequencing of human Langerhans cells identifies altered gene expression profiles in patients with atopic dermatitis"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6194-2400","authenticated-orcid":false,"given":"Sara M","family":"Tamminga","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC location University of Amsterdam , Amsterdam,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Marlot","family":"Van Der Wal","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht, Utrecht University , Utrecht,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3147-5431","authenticated-orcid":false,"given":"Elise S","family":"Saager","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht, Utrecht University , Utrecht,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7981-7771","authenticated-orcid":false,"given":"Lian F","family":"Van Der Gang","sequence":"additional","affiliation":[{"name":"National Expertise Center for Atopic Dermatitis, Department of Dermatology and Allergology, University Medical Center Utrecht , Utrecht,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3371-6414","authenticated-orcid":false,"given":"Celeste M","family":"Boesjes","sequence":"additional","affiliation":[{"name":"National Expertise Center for Atopic Dermatitis, Department of Dermatology and Allergology, University Medical Center Utrecht , Utrecht,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9014-0014","authenticated-orcid":false,"given":"Astrid","family":"Hendriks","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC location University of Amsterdam , Amsterdam,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Pannekoek","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC location University of Amsterdam , Amsterdam,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolein S","family":"De Bruin","sequence":"additional","affiliation":[{"name":"National Expertise Center for Atopic Dermatitis, Department of Dermatology and Allergology, University Medical Center Utrecht , Utrecht,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femke","family":"Van Wijk","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht, Utrecht University , Utrecht,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2695-5863","authenticated-orcid":false,"given":"Nina M","family":"Van Sorge","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC location University of Amsterdam , Amsterdam,","place":["the Netherlands"]},{"name":"Netherlands Reference Laboratory for Bacterial Meningitis, Amsterdam UMC location AMC , Amsterdam,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"key":"2025012409003401200_vlae009-B1","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1038\/jid.2013.446","article-title":"The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions","volume":"134","author":"Hay","year":"2014","journal-title":"J Invest Dermatol"},{"key":"2025012409003401200_vlae009-B2","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jid.2019.05.024","article-title":"IL-4Ralpha blockade by dupilumab decreases Staphylococcus aureus colonization and increases microbial diversity in atopic dermatitis","volume":"140","author":"Callewaert","year":"2020","journal-title":"J Invest Dermatol"},{"key":"2025012409003401200_vlae009-B3","doi-asserted-by":"crossref","first-page":"4703","DOI":"10.1038\/s41467-019-12253-y","article-title":"Microbe-host interplay in atopic dermatitis and psoriasis","volume":"10","author":"Fyhrquist","year":"2019","journal-title":"Nat Commun"},{"key":"2025012409003401200_vlae009-B4","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1056\/NEJMoa1314768","article-title":"Dupilumab treatment in adults with moderate-to-severe atopic dermatitis","volume":"371","author":"Beck","year":"2014","journal-title":"N Engl J Med"},{"key":"2025012409003401200_vlae009-B5","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1093\/bjd\/ljae138","article-title":"Blockade of IL-13 signaling improves skin barrier function and biology in patients with moderate to severe atopic dermatitis","volume":"191","author":"Sander","year":"2024","journal-title":"Br J Dermatol"},{"key":"2025012409003401200_vlae009-B6","doi-asserted-by":"crossref","first-page":"720674","DOI":"10.3389\/fcimb.2021.720674","article-title":"The skin microbiome of patients with atopic dermatitis normalizes gradually during treatment","volume":"11","author":"Khadka","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"2025012409003401200_vlae009-B7","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1016\/j.jid.2024.01.011","article-title":"Adding Fuel to the Fire? The Skin Microbiome in Atopic Dermatitis","volume":"144","author":"Saheb Kashaf","year":"2024","journal-title":"J Invest Dermatol"},{"key":"2025012409003401200_vlae009-B8","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aal4651","article-title":"Staphylococcus aureus and Staphylococcus epidermidis strain diversity underlying pediatric atopic dermatitis","volume":"9","author":"Byrd","year":"2017","journal-title":"Sci Transl Med"},{"key":"2025012409003401200_vlae009-B9","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.tim.2017.11.008","article-title":"Staphylococcus aureus and atopic dermatitis: a complex and evolving relationship","volume":"26","author":"Geoghegan","year":"2018","journal-title":"Trends Microbiol"},{"key":"2025012409003401200_vlae009-B10","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.alit.2019.02.006","article-title":"Staphylococcus aureus in atopic dermatitis: strain-specific cell wall proteins and skin 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lymphoma","volume":"172","author":"Hanafusa","year":"2013","journal-title":"Clin Exp Immunol"},{"key":"2025012409003401200_vlae009-B39","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/S1081-1206(10)60170-6","article-title":"Expansion of FOXP3-positive CD4+CD25+ T cells associated with disease activity in atopic dermatitis","volume":"103","author":"Ito","year":"2009","journal-title":"Ann Allergy Asthma Immunol"},{"key":"2025012409003401200_vlae009-B40","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1111\/j.1365-2133.2009.09035.x","article-title":"Regulatory T cells in atopic dermatitis: epidermal dendritic cell clusters may contribute to their local expansion","volume":"160","author":"Szegedi","year":"2009","journal-title":"Br J Dermatol"},{"key":"2025012409003401200_vlae009-B41","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.immuni.2012.03.018","article-title":"Human epidermal Langerhans cells maintain immune homeostasis in skin by 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factors other than superantigens be involved?","volume":"33","author":"Rojo","year":"2014","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2025012409003401200_vlae009-B51","doi-asserted-by":"crossref","first-page":"e00994","DOI":"10.1128\/IAI.00994-16","article-title":"Clumping factor B promotes adherence of Staphylococcus aureus to corneocytes in atopic dermatitis","volume":"85","author":"Fleury","year":"2017","journal-title":"Infect Immun"},{"key":"2025012409003401200_vlae009-B52","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1248\/bpb.b14-00614","article-title":"CCL17 production by mouse langerhans cells stimulated with Staphylococcus aureus cell wall components","volume":"38","author":"Matsui","year":"2015","journal-title":"Biol Pharm Bull"},{"key":"2025012409003401200_vlae009-B53","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/j.jaci.2023.05.026","article-title":"Rapid reduction in Staphylococcus aureus in atopic dermatitis subjects following dupilumab treatment","volume":"152","author":"Simpson","year":"2023","journal-title":"J Allergy Clin Immunol"},{"key":"2025012409003401200_vlae009-B54","doi-asserted-by":"crossref","first-page":"3841","DOI":"10.1007\/s00018-019-03393-x","article-title":"Exotoxins from Staphylococcus aureus activate 5-lipoxygenase and induce leukotriene biosynthesis","volume":"77","author":"Romp","year":"2020","journal-title":"Cell Mol Life Sci"},{"key":"2025012409003401200_vlae009-B55","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/j.1365-2222.2011.03857.x","article-title":"Low neonatal Toll-like receptor 4-mediated interleukin-10 production is associated with subsequent atopic dermatitis","volume":"42","author":"Belderbos","year":"2012","journal-title":"Clin Exp Allergy"},{"key":"2025012409003401200_vlae009-B56","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1159\/000492130","article-title":"Low interleukin 10 production at birth is a risk factor for atopic 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