{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:53:51Z","timestamp":1793145231337,"version":"4.5.0"},"reference-count":88,"publisher":"American Society for Clinical Investigation","issue":"3","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":55,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R56-AI165769,R01-AI123539"],"award-info":[{"award-number":["R56-AI165769,R01-AI123539"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,10]]},"abstract":"<jats:p>\n                    In systemic lupus erythematosus (lupus), environmental effects acting within a permissive genetic background lead to autoimmune dysregulation. Dysfunction of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells contributes to pathology by providing help to autoreactive B and T cells, and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell dysfunction coincides with altered DNA methylation and histone modifications of select gene loci. However, chromatin accessibility states of distinct T cell subsets and mechanisms driving heterogeneous chromatin states across patients remain poorly understood. We defined the transcriptome and epigenome of multiple CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell populations from patients with lupus and healthy individuals. Most patients with lupus, regardless of disease activity, had enhanced chromatin accessibility bearing hallmarks of inflammatory cytokine signals. Single-cell approaches revealed that chromatin changes extended to naive CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, uniformly affecting naive subpopulations. Transcriptional data and cellular and protein analyses suggested that the TNF family members, TNF-\u03b1, LIGHT, and TWEAK, were linked to observed molecular changes and the altered lupus chromatin state. However, we identified a patient subgroup prescribed angiotensin receptor blockers (ARBs), which lacked TNF-linked lupus chromatin accessibility features. These data raise questions about the role of lupus-associated chromatin changes in naive CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell activation and differentiation and implicate ARBs in the regulation of disease-driven epigenetic states.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.176811","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T12:00:37Z","timestamp":1734436837000},"source":"Crossref","is-referenced-by-count":2,"title":["Angiotensin receptor blockers modulate the lupus CD4+ T cell epigenome characterized by TNF family\u2013linked signaling"],"prefix":"10.1172","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4821-7834","authenticated-orcid":true,"given":"Andrew P.","family":"Hart","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, and"},{"name":"Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan J.","family":"Kotzin","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, and"},{"name":"Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffan W.","family":"Schulz","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan S.","family":"Dunham","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison L.","family":"Keenan","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua F.","family":"Baker","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, and"},{"name":"Division of Rheumatology, Department of Medicine, Corporal Michael J. 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