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

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. ([e-mail]) with appropriate institutional approvals.]]>
Subjects were recruited through RALLY at Massachusetts General Hospital (MGH), an online platform that connects the public with research opportunities at MGH. Sample and clinical data collection was conducted in accordance with protocols approved by Institutional Review Boards at MGH (protocol number 2018P002325) and Boston Children's Hospital (protocol number P00001109). Inclusion Criteria Subjects at least 18 years of age or older (for the adult recruitment at MGH). A confirmed diagnosis of an inflammatory or autoimmune skin disorder, such as atopic dermatitis, morphea, neutrophilic dermatosis, or scleroderma. Presence of an active lesion of the above diagnosis. For the healthy subjects, those with an inflammatory skin disorder were excluded. Exclusion Criteria Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study. History of poor wound healing or blood-clotting abnormality. History of keloid formation or hypertrophic scarring. Regular intake of high doses of aspirin or anti-coagulant medications. Hypersensitivity to local anesthetics. History of poorly controlled diabetes mellitus. Pregnancy (for the adult recruitment at MGH). ]]>
This is a case-control study of subjects with and without inflammatory skin conditions (atopic dermatitis, scleroderma). The first subject was enrolled in May 2019 and the last subject was enrolled in January 2025.]]>