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Adv."],"published-print":{"date-parts":[[2026,7,10]]},"abstract":"<jats:p>\n                    Type 1 regulatory T (Tr1) cells are CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells with suppressive function that are induced from conventional T cells exposed to persistent or strong antigens. Human Tr1 cells are understudied; the regulators of their antigen-driven differentiation are unknown, and identifying them in tissues, where antigen interactions occur, is challenging. Here, we conducted a multiomic profiling of human antigen-induced Tr1 cells. Using CRISPR-based functional genomics, we uncovered essential roles of transcription factors IRF4, BATF, and MAF in human Tr1 differentiation, phenotype, and function. We also derived a Tr1 transcriptional signature that detects cells with a Tr1 phenotype in single-cell datasets from patients treated with Tr1 therapy and those with solid tumors. Cross-species analysis confirmed this signature identifies bona fide Tr1 cells induced in vivo in a murine solid tumor model. These findings provide a framework for development of Tr1-based and Tr1-targeting therapies and studies of Tr1 cell biology.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aec6358","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T17:58:37Z","timestamp":1783706317000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic landscape, key transcriptional regulators, and in vivo identification of human Tr1 cells"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2862-1901","authenticated-orcid":true,"given":"Alma-Martina","family":"Cepika","sequence":"first","affiliation":[{"name":"Division of General Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA."},{"name":"Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University 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