<p>In atopic dermatitis (AD) patients, the homeostatic processes maintaining barrier integrity and immune regulation in the skin break down, resulting in chronic inflammation. To understand the tissue changes occurring during disease, we profiled skin from AD, scleroderma, and healthy patients using single-cell transcriptomics (scRNA-Seq) and immune repertoire profiling of TCR sequences (scV(D)J-Seq). We included scleroderma as another case of skin disorder to compare with AD. We profiled single cells from whole skin tissue of 6 healthy individuals, 2 individuals with scleroderma, and 8 individuals with AD, including non-lesional and lesional skin, allowing us to identify characteristic cell type compositions, cell states, and differentiation programs in the AD tissue microenvironment. We further integrated this with single-cell profiles from four public studies into a comprehensive human skin cell atlas. The joint profiling of transcriptomes and TCR sequences also identified a unique, clonally expanded T cell state in lesional skin that had characteristics of both type 2 and type 17 immunity. Finally, we identified two specific multicellular immune/stromal communities that impact aberrant keratinocyte differentiation in AD. In this dbGaP study, we provide the raw sequences for samples profiled by scRNA-Seq and scV(D)J-Seq. Raw sequences for pediatric samples cannot be deposited in a public repository because of restrictions in the informed consent, and may be requested from L.S. (<a href="lynda.Schneider@childrens.harvard.edu">lynda.Schneider@childrens.harvard.edu</a>) with appropriate institutional approvals.</p>

Studies of Atopic Dermatitis through Single-Cell Transcriptomics and Immune Repertoires

Multi-modal skin atlas identifies a multicellular immune-stromal community associated with altered cornification and specific T cell expansion in atopic dermatitis