Developmental cell programs are co-opted in inflammatory skin disease
- 22 January 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 371 (6527), 364-+
- https://doi.org/10.1126/science.aba6500
Abstract
The skin confers biophysical and immunological protection through a complex cellular network established early in embryonic development. We profiled the transcriptomes of more than 500,000 single cells from developing human fetal skin, healthy adult skin, and adult skin with atopic dermatitis and psoriasis. We leveraged these datasets to compare cell states across development, homeostasis, and disease. Our analysis revealed an enrichment of innate immune cells in skin during the first trimester and clonal expansion of disease-associated lymphocytes in atopic dermatitis and psoriasis. We uncovered and validated in situ a reemergence of prenatal vascular endothelial cell and macrophage cellular programs in atopic dermatitis and psoriasis lesional skin. These data illustrate the dynamism of cutaneous immunity and provide opportunities for targeting pathological developmental programs in inflammatory skin diseases.Keywords
Funding Information
- Wellcome (WT107931/Z/15/Z)
- Wellcome (WT211276/Z/18/Z)
- Wellcome (WT206194)
- Wellcome
- Wellcome (211276/E/18/Z)
- Wellcome (206439/Z/17/Z)
- Wellcome (108874/Z/15/Z)
- Medical Research Council (MR/R006237/1)
- Lister Institute of Preventive Medicine
- NIHR Newcastle Biomedical Research Centre
- Wellcome (WT214539/Z/18/Z)
- Medical Research Council UK, NIHR Oxford Biomedical Research Centre and NIHR Clinical Research Network
- NIHR Biomedical Research Centre, Guy’s and St Thomas’ NHS Foundation Trust
- Chan Zuckerberg Initiative (2017-173808)
- Medical Research Council (MR/PO18823/1)
- Wellcome (296194)
- Cancer Research UK (C609/A27326)
- NIHR Newcastle Biomedical Research Centre
This publication has 88 references indexed in Scilit:
- Human Tissues Contain CD141hi Cross-Presenting Dendritic Cells with Functional Homology to Mouse CD103+ Nonlymphoid Dendritic CellsImmunity, 2012
- Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac–derived macrophagesThe Journal of Experimental Medicine, 2012
- Interferon-stimulated genes and their antiviral effector functionsCurrent Opinion in Virology, 2011
- DUSP4 deficiency enhances CD25 expression and CD4+ T‐cell proliferation without impeding T‐cell developmentEuropean Journal of Immunology, 2011
- Disease Ontology: a backbone for disease semantic integrationNucleic Acids Research, 2011
- Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC networkThe Journal of Experimental Medicine, 2009
- Th17 Cytokines Stimulate CCL20 Expression in Keratinocytes In Vitro and In Vivo: Implications for Psoriasis PathogenesisJournal of Investigative Dermatology, 2009
- Blimp Hovers over T Cell ImmunityImmunity, 2009
- Toward unraveling the complexity of simple epithelial keratins in human diseaseJCI Insight, 2009
- Differential rates of replacement of human dermal dendritic cells and macrophages during hematopoietic stem cell transplantationThe Journal of Experimental Medicine, 2009