Gary Reynolds, Peter Vegh, James Fletcher, Elizabeth F. M. Poyner, Emily Stephenson, Issac Goh, Rachel A. Botting, Ni Huang, Bayanne Olabi, Anna Dubois, David Dixon, Kile Green, Daniel Maunder, Justin Engelbert, Mirjana Efremova, Krzysztof Polanski, Laura Jardine, Claire Jones, Thomas Ness, Dave Horsfall, Jim McGrath, Christopher Carey, Dorin-Mirel Popescu, Simone Webb, Xiao-nong Wang, Ben Sayer, Jong-Eun Park, Victor A. Negri, Daria Belokhvostova, Magnus D. Lynch, David McDonald, Andrew Filby, Tzachi Hagai, Kerstin B. Meyer, Akhtar Husain, Jonathan Coxhead, Roser Vento-Tormo, Sam Behjati, Steven Lisgo, Alexandra-Chloe Villani, Jaume Bacardit, Philip H. Jones, Edel A. O’Toole, Graham S. Ogg, Neil Rajan, Nick J. Reynolds, Sarah A. Teichmann, Fiona M. Watt, Muzlifah Haniffa
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.