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How this network reorganizes to safeguard epidermal immunity after injury has remained unclear. Here, we uncover a previously unrecognized two-lineage program of LC repopulation during wound repair. Classically, tissue-resident embryonically derived LCs (eLCs) migrate to lymph nodes in response to antigens. In contrast, we find that injury triggers nearby eLCs to migrate into wounds, providing immediate coverage. In parallel, circulating monocytes infiltrate the skin and differentiate into long-lived monocyte-derived LCs (mLCs) that integrate stably into the network. We identify the chemokine receptor CXCR2 as a novel regulator of eLC migration into wounds, distinct from the CXCR4\/CCR7 pathways mediating LC egress to lymph nodes. Pharmacological inhibition of CXCR2 impairs directional eLC migration and is accompanied by increased mLC infiltration, preserving immune barrier density. These findings reveal a coordinated and flexible two-lineage repair program that ensures robust restoration of epidermal immunity.<\/jats:p>","DOI":"10.64898\/2026.05.25.727646","type":"posted-content","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T17:50:18Z","timestamp":1779990618000},"source":"Crossref","is-referenced-by-count":0,"title":["Dual lineages of Langerhans cells cooperate to restore the immune barrier after skin injury"],"prefix":"10.64898","author":[{"given":"Axel D.","family":"Schmitter-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Institute for Quantitative Health Science and Engineering (IQ), Michigan State University, East Lansing, MI, USA"},{"name":"Cell and Molecular Biology Program, College of Natural Science, Michigan State University, East Lansing, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Basista","sequence":"additional","affiliation":[{"name":"Institute for Quantitative Health Science and Engineering (IQ), Michigan State University, East Lansing, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6997-1302","authenticated-orcid":false,"given":"Sudhanshu","family":"Mishra","sequence":"additional","affiliation":[{"name":"Institute for Quantitative Health Science and Engineering (IQ), Michigan State University, East Lansing, MI, USA"},{"name":"Cell and Molecular Biology Program, College of Natural Science, Michigan State University, East Lansing, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0832-3096","authenticated-orcid":false,"given":"Hyeri","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute for Quantitative Health Science and Engineering (IQ), Michigan State University, East Lansing, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Bench","sequence":"additional","affiliation":[{"name":"Institute for Quantitative Health Science and Engineering (IQ), Michigan State University, East Lansing, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Matte-Martone","sequence":"additional","affiliation":[{"name":"Department of Genetics, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Soo","family":"Seo","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Kyungpook National University, Daegu 41566, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gun Woo","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute for Quantitative Health Science and Engineering (IQ), Michigan State University, East Lansing, MI, USA"},{"name":"Department of Orthopedic Surgery, Ulsan Medical Center, Ulsan 44686, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8329-5104","authenticated-orcid":false,"given":"Sangbum","family":"Park","sequence":"additional","affiliation":[{"name":"Institute for Quantitative Health Science and Engineering (IQ), Michigan State University, East Lansing, MI, USA"},{"name":"Division of Dermatology, Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, MI, USA"},{"name":"Department of Pharmacology and Toxicology, College of Human Medicine, Michigan State University, East Lansing, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026072819550694000_2026.05.25.727646v2.1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3646"},{"key":"2026072819550694000_2026.05.25.727646v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2017.10.001"},{"key":"2026072819550694000_2026.05.25.727646v2.3","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3472"},{"key":"2026072819550694000_2026.05.25.727646v2.4","doi-asserted-by":"publisher","DOI":"10.1038\/nature07039"},{"key":"2026072819550694000_2026.05.25.727646v2.5","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3815"},{"key":"2026072819550694000_2026.05.25.727646v2.6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02638"},{"key":"2026072819550694000_2026.05.25.727646v2.7","doi-asserted-by":"crossref","unstructured":"Appios, A. et al. 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