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Adv."],"published-print":{"date-parts":[[2026,8,14]]},"abstract":"<jats:p>The mouse epidermis harbors two key resident immune populations\u2014dendritic epidermal T cells (DETCs), a subset of invariant \u03b3\u03b4 T cells, and Langerhans cells (LCs), specialized tissue-resident macrophages\u2014both of which play critical roles in immune surveillance, barrier integrity, and tissue homeostasis. While their fetal origin has been defined, the mechanisms governing their postnatal maturation remain poorly understood. Here, we present a combined immunophenotypic and single-cell transcriptomic map of DETC and LC development from late embryogenesis through adulthood in mice. We delineate distinct differentiation trajectories characterized by dynamic changes in morphology, proliferation, and transcriptional programming. Using \u03b3\u03b4 T cell deficient mice, we show that LC maturation proceeds independently of canonical \u03b3\u03b4DETCs, likely due to compensatory \u03b1\u03b2DETCs. Analysis of germfree mice and wildlings further demonstrates that the postnatal DETC and LC differentiation is independent of microbial colonization. Comparative analysis with developing human epidermis reveals partially conserved differentiation programs. Together, our findings define core principles underlying establishment of the epidermal immune niche.<\/jats:p>","DOI":"10.1126\/sciadv.aec9180","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T17:58:41Z","timestamp":1786730321000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Distinct postnatal trajectories of mouse dendritic epidermal T cells and Langerhans cells independent of microbiota"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0011-073X","authenticated-orcid":true,"given":"David","family":"Obwegs","sequence":"first","affiliation":[{"name":"Department of Medicine II, Faculty of Medicine, Medical Center\u2013University of Freiburg, 79106 Freiburg, Germany."},{"name":"Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Oschwald","sequence":"additional","affiliation":[{"name":"Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany."},{"name":"Institute of Neuropathology, Faculty of Medicine, Medical Center\u2013University of Freiburg, 79106 Freiburg, Germany."},{"name":"Institute for Infection Prevention and Control, Faculty of Medicine, Medical Center\u2013University of Freiburg, 79106 Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara M.","family":"Koetter","sequence":"additional","affiliation":[{"name":"Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany."},{"name":"Institute of Neuropathology, Faculty of Medicine, Medical Center\u2013University of Freiburg, 79106 Freiburg, Germany."},{"name":"Institute for Infection Prevention and Control, Faculty of Medicine, Medical Center\u2013University of Freiburg, 79106 Freiburg, 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Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2705-5685","authenticated-orcid":true,"given":"Christian","family":"Koengeter","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Faculty of Medicine, Medical Center\u2013University of Freiburg, 79106 Freiburg, Germany."},{"name":"Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2561-0820","authenticated-orcid":true,"given":"Anna-Maria","family":"Schaffer","sequence":"additional","affiliation":[{"name":"Department of Synthetic Immunology, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany."},{"name":"Centre for Chronic Immunodeficiency (CCI), Faculty of Medicine, University of Freiburg, 79106 Freiburg, 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