Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity
Langerhans cells (LCs) are distinct among phagocytes, functioning both as embryo-derived, tissue-resident macrophages in skin innervation and repair and as migrating professional antigen-presenting cells, a function classically assigned to dendritic cells (DCs). Here, we demonstrate that both intrinsic and extrinsic factors imprint this dual identity. Using ablation of embryo-derived LCs in the murine adult skin and tracking differentiation of incoming monocyte-derived replacements, we found intrinsic intraepidermal heterogeneity. We observed that ontogenically distinct monocytes give rise to LCs. Within the epidermis, Jagged-dependent activation of Notch signaling, likely within the hair follicle niche, provided an initial site of LC commitment before metabolic adaptation and survival of monocyte-derived LCs. In the human skin, embryo-derived LCs in newborns retained transcriptional evidence of their macrophage origin, but this was superseded by DC-like immune modules after postnatal expansion. Thus, adaptation to adult skin niches replicates conditioning of LC at birth, permitting repair of the embryo-derived LC network.
Authors
- James Davies (ORCID: https://orcid.org/0000-0002-4177-8842)
- Michael R. Ardern‐Jones (ORCID: https://orcid.org/0000-0003-1466-2016)
- Andrés F. Vallejo (ORCID: https://orcid.org/0000-0002-4688-0598)
- Zhaoyuan Liu (ORCID: https://orcid.org/0000-0002-3117-0833)
- Sébastien Trzebanski (ORCID: https://orcid.org/0000-0002-0647-6814)
- Cyril Carvalho (ORCID: https://orcid.org/0000-0001-7125-3521)
- Marlène Magalhaes Pinto (ORCID: https://orcid.org/0000-0002-1656-8747)
- Marta E. Polak (ORCID: https://orcid.org/0000-0003-2878-476X)
- Johannes Schroth (ORCID: https://orcid.org/0000-0003-2457-0246)
- Clare L. Bennett (ORCID: https://orcid.org/0000-0001-9146-2347)
- Elaine Emmerson (ORCID: https://orcid.org/0000-0002-5902-3368)
- Florent Ginhoux (ORCID: https://orcid.org/0000-0002-2857-7755)
- Anna Appios (ORCID: https://orcid.org/0000-0002-7111-5126)
- Stephen Henderson (ORCID: https://orcid.org/0000-0002-9032-3828)
- Rebecca Gentek (ORCID: https://orcid.org/0000-0001-6574-7242)
- Siân M. Henson (ORCID: https://orcid.org/0000-0003-1893-4912)
- Steffen Jung (ORCID: https://orcid.org/0000-0003-4290-5716)
- Nigel Hall (ORCID: https://orcid.org/0000-0001-8570-9374)
- Sofía Sirvent (ORCID: https://orcid.org/0000-0003-0050-8579)
- Shreya Lovlekar
- Howard Yuan-Hao Kan (ORCID: https://orcid.org/0009-0005-5382-848X)
- Morven L. Law (ORCID: https://orcid.org/0009-0005-7135-8346)
- Inês Boal Carvalho
- C Major
Institutions
- Agency for Science, Technology and Research (SG)
- Inserm (FR)
- Shanghai Jiao Tong University (CN)
- Singapore Immunology Network (SG)
- Institut Gustave Roussy (FR)
- University Hospital Southampton NHS Foundation Trust (GB)
- MRC Centre for Regenerative Medicine (GB)
- MRC Centre for Reproductive Health (GB)
- William Harvey Research Institute (GB)
- University of Southampton (GB)
- University College London (GB)
- Weizmann Institute of Science (IL)
- University of Edinburgh (GB)
Publication Details
- Journal
- Science Immunology
- Published
- 2024-09-06
- DOI
- https://doi.org/10.1126/sciimmunol.adp0344
- Citations
- 8
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 1.92
Funders
- Wellcome Trust
- UK Research and Innovation
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council