Distinct postnatal trajectories of mouse dendritic epidermal T cells and Langerhans cells independent of microbiota
The mouse epidermis harbors two key resident immune populations-dendritic epidermal T cells (DETCs), a subset of invariant γδ T cells, and Langerhans cells (LCs), specialized tissue-resident macrophages-both 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 γδ T cell deficient mice, we show that LC maturation proceeds independently of canonical γδDETCs, likely due to compensatory αβDETCs. 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.
Authors
- Stephan P. Rosshart (ORCID: https://orcid.org/0000-0002-6989-8686)
- Philipp Henneke (ORCID: https://orcid.org/0000-0001-7314-7984)
- Solveig Runge (ORCID: https://orcid.org/0000-0002-9193-476X)
- Marleen Eckert (ORCID: https://orcid.org/0009-0003-2019-2601)
- Marco Prinz (ORCID: https://orcid.org/0000-0002-0349-1955)
- Kerstin Bruder
- Daniel Erny (ORCID: https://orcid.org/0000-0001-6000-8838)
- Wolfgang W. Schamel (ORCID: https://orcid.org/0000-0003-4496-3100)
- Anna-Maria Schaffer (ORCID: https://orcid.org/0000-0002-2561-0820)
- Katrin Kierdorf (ORCID: https://orcid.org/0000-0002-9272-4780)
- Sophia Papaioannou (ORCID: https://orcid.org/0000-0003-1857-6465)
- Julia Kolter (ORCID: https://orcid.org/0000-0002-3268-8124)
- Lukas Amann (ORCID: https://orcid.org/0000-0002-8363-373X)
- Vidmante Fuchs (ORCID: https://orcid.org/0000-0002-6878-1793)
- Susana Minguet (ORCID: https://orcid.org/0000-0001-8211-5538)
- David Obwegs (ORCID: https://orcid.org/0009-0009-0011-073X)
- Cylia Crisand
- Nisreen Ghanem
- Alexander Oschwald
- Lara M. Koetter
- Sidney Doerr
- Sagar (ORCID: https://orcid.org/0000-0002-8657-4704)
- Tim Rollenske (ORCID: https://orcid.org/0000-0002-7921-4778)
- Christian Koengeter (ORCID: https://orcid.org/0009-0003-2705-5685)
Institutions
- University of Freiburg (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- University Hospital Bonn (DE)
- University Medical Center Freiburg (DE)
- LMU Klinikum (DE)
- Universitätsklinikum Erlangen (DE)
- Bernstein Center for Computational Neuroscience Freiburg (DE)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Science Advances
- Published
- 2026-08-14
- DOI
- https://doi.org/10.1126/sciadv.aec9180
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Deutsche Forschungsgemeinschaft
- Albert-Ludwigs-Universität Freiburg