{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T16:17:24Z","timestamp":1782836244425,"version":"3.54.5"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T00:00:00Z","timestamp":1658793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["K08AR067243"],"award-info":[{"award-number":["K08AR067243"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003980","name":"National Eczema Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003980","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003185","name":"National Psoriasis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003185","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013671","name":"Sun Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013671","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Identifying genetic variation underlying human diseases establishes targets for therapeutic development and helps tailor treatments to individual patients. Large-scale transcriptomic profiling has extended the study of such molecular heterogeneity between patients to somatic tissues. However, the lower resolution of bulk RNA profiling, especially in a complex, composite tissue such as the skin, has limited its success. Here we demonstrate approaches to interrogate patient-level molecular variance in a chronic skin inflammatory disease, psoriasis vulgaris, leveraging single-cell RNA-sequencing of CD45<jats:sup>+<\/jats:sup> cells isolated from active lesions. Highly psoriasis-specific transcriptional abnormalities display greater than average inter-individual variance, nominating them as potential sources of clinical heterogeneity. We find that one of these chemokines, <jats:italic>CXCL13<\/jats:italic>, demonstrates significant correlation with severity of lesions within our patient series. Our analyses also establish that genes elevated in psoriatic skin-resident memory T cells are enriched for programs orchestrating chromatin and CDC42-dependent cytoskeleton remodeling, specific components of which are distinctly correlated with and against Th17 identity on a single-cell level. Collectively, these analyses describe systematic means to dissect cell type- and patient-level differences in cutaneous psoriasis using high-resolution transcriptional profiles of human inflammatory disease.<\/jats:p>","DOI":"10.3389\/fimmu.2022.842651","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T05:36:53Z","timestamp":1658813813000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Defining Patient-Level Molecular Heterogeneity in Psoriasis Vulgaris Based on Single-Cell 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