{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:23:19Z","timestamp":1791912199846,"version":"4.3.4"},"reference-count":84,"publisher":"American Society for Clinical Investigation","issue":"17","license":[{"start":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T00:00:00Z","timestamp":1725321600000},"content-version":"vor","delay-in-days":42,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["DP5 OD023091,R21 AI150657"],"award-info":[{"award-number":["DP5 OD023091,R21 AI150657"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001582","name":"Dermatology Foundation","doi-asserted-by":"crossref","award":["Diversity Research Supplement Award"],"award-info":[{"award-number":["Diversity Research Supplement Award"]}],"id":[{"id":"10.13039\/100001582","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Sun Pharma\/SID","award":["Innovation Research Fellowship"],"award-info":[{"award-number":["Innovation Research Fellowship"]}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["423175926,GZ: SCHU 3377\/1-1"],"award-info":[{"award-number":["423175926,GZ: SCHU 3377\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,3]]},"abstract":"<jats:p>\n                    Delayed-type drug hypersensitivity reactions are major causes of morbidity and mortality. The origin, phenotype, and function of pathogenic T cells across the spectrum of severity require investigation. We leveraged recent technical advancements to study skin-resident memory T cells (TRMs) versus recruited T cell subsets in the pathogenesis of severe systemic forms of disease, Stevens-Johnson syndrome\/toxic epidermal necrolysis (SJS\/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS), and skin-limited disease, morbilliform drug eruption (MDE). Microscopy, bulk transcriptional profiling, and single-cell RNA-sequencing (scRNA-Seq) plus cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq) plus T cell receptor sequencing (TCR-Seq) supported clonal expansion and recruitment of cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells from circulation into skin along with expanded and nonexpanded cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    skin TRM in SJS\/TEN. Comparatively, MDE displayed a cytotoxic T cell profile in skin without appreciable expansion and recruitment of cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells from circulation, implicating TRMs as potential protagonists in skin-limited disease. Mechanistic interrogation in patients unable to recruit T cells from circulation into skin and in a parallel mouse model supported that skin TRMs were sufficient to mediate MDE. Concomitantly, SJS\/TEN displayed a reduced Treg signature compared with MDE. DRESS demonstrated recruitment of cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells into skin as in SJS\/TEN, yet a pro-Treg signature as in MDE. These findings have important implications for fundamental skin immunology and clinical care.\n                  <\/jats:p>","DOI":"10.1172\/jci178253","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T12:06:38Z","timestamp":1721736398000},"source":"Crossref","is-referenced-by-count":21,"title":["Systemic and skin-limited delayed-type drug hypersensitivity reactions associate with distinct resident and recruited T cell subsets"],"prefix":"10.1172","volume":"134","author":[{"given":"Pranali N.","family":"Shah","sequence":"first","affiliation":[{"name":"Department of Dermatology, Brigham and Women\u2019s Hospital (BWH), Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A.","family":"Romar","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Brigham and Women\u2019s Hospital (BWH), Harvard Medical School, Boston, Massachusetts, 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