Developmental cell programs are co-opted in inflammatory skin disease.
Gary ReynoldsPeter VeghJames FletcherElizabeth F M PoynerEmily StephensonIssac GohRachel Anne BottingNi HuangBayanne OlabiAnna DuboisDavid DixonKile GreenDaniel MaunderJustin EngelbertMirjana EfremovaKrzysztof PolańskiLaura JardineClaire J JonesThomas NessDavid HorsfallJim McGrathChristopher D CareyDorin-Mirel PopescuSimone WebbXiao-Nong WangBen SayerJong-Eun ParkVictor A NegriDaria BelokhvostovaMagnus D LynchDavid McDonaldAndrew FilbyTzachi HagaiKerstin B MeyerAkhtar HusainJonathan CoxheadRoser Vento-TormoSam BehjatiSteven N LisgoAlexandra-Chloé VillaniJaume BacarditPhilip H JonesEdel A O'TooleGraham S OggNeil RajanNick J ReynoldsSarah A TeichmannFiona M WattMuzlifah A HaniffaPublished in: Science (New York, N.Y.) (2021)
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.