{ "abstract": "Regulatory T cells (Treg cells) maintain immune tolerance, but how broadly acting epigenetic pathways are selectively used by Treg cells versus conventional T cells (Tconv cells) remains unclear. Here, we identify the COMPASS-trimethylation of histone H3 lysine 4 (H3K4me3) pathway, through its Wdr82 component, as a key epigenetic regulator that preferentially supports Treg cell development and function. Although Wdr82 deficiency broadly impairs T cell activation, T cell-specific deletion paradoxically causes progressive, microbiota-dependent intestinal inflammation and expansion of inflammatory Tconv cell programs. This pathology is prevented by microbiome depletion or transfer of wild-type Treg cells, indicating a primary defect in Treg cell-mediated tolerance. Mechanistically, Wdr82/COMPASS promotes Foxp3 induction, maintains H3K4me3 and chromatin accessibility at Treg cell-associated genes, and restrains effector programs within the Treg cell lineage. Foxp3 coordinates with COMPASS components in a T cell receptor/costimulation-dependent manner, linking antigen receptor signaling to chromatin regulation. Together, these findings reveal selective integration of a broadly active epigenetic pathway into the Foxp3-centered regulatory hierarchy that sustains Treg cell control of microbiota-driven intestinal inflammation.", "abstract_shown": true, "affiliations": [ "Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.", "Center for Applied Bioinformatics, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.", "Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.", "Center for Advanced Genome Engineering, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.", "Center for Proteomics and Metabolomics, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.", "Department of Tumor Cell Biology, 4, Memphis, TN 38105, USA." ], "article_type": "Research Article", "arxiv": null, "author_total": 22, "authors": [ { "affs": [ 0 ], "name": "Wenjun Huang", "orcid": "0009-0005-0002-3426" }, { "affs": [ 0 ], "name": "Jun Li", "orcid": "0000-0002-2611-8918" }, { "affs": [ 0 ], "name": "Minghong He", "orcid": "0000-0001-9978-7218" }, { "affs": [ 1 ], "name": "Beisi Xu", "orcid": "0000-0003-0099-858X" }, { "affs": [ 1 ], "name": "Wojciech Rosikiewicz", "orcid": "0000-0001-7031-3430" }, { "affs": [ 0 ], "name": "Xiaolei Hao", "orcid": "0000-0003-3413-2338" }, { "affs": [ 0 ], "name": "Menglin Jiang", "orcid": "0000-0002-1660-9916" }, { "affs": [ 0 ], "name": "Lu Bai", "orcid": "0000-0002-8779-336X" }, { "affs": [ 1 ], "name": "Siwei Zhang", "orcid": "0000-0002-1646-063X" }, { "affs": [ 1 ], "name": "Lei Li", "orcid": "0000-0002-8828-5199" }, { "affs": [ 1 ], "name": "Wenjie Qi" }, { "affs": [ 0 ], "name": "Vivek Choudhary" }, { "affs": [ 0 ], "name": "Min-Jhen Jheng" }, { "affs": [ 1 ], "name": "Ti-Cheng Chang", "orcid": "0000-0001-5302-9147" }, { "affs": [ 2 ], "name": "Laura J. Janke", "orcid": "0000-0002-9871-6239" }, { "affs": [ 3 ], "name": "Shondra M. Pruett-Miller", "orcid": "0000-0002-3793-585X" }, { "affs": [ 4 ], "name": "Kiran Kodali", "orcid": "0000-0002-0854-1405" }, { "affs": [ 4 ], "name": "Zuo-Fei Yuan", "orcid": "0000-0003-1252-6766" }, { "affs": [ 4 ], "name": "Anthony A. High", "orcid": "0000-0003-2323-5649" }, { "affs": [ 1 ], "name": "Hongjian Jin", "orcid": "0000-0003-3833-7170" }, { "affs": [ 5 ], "name": "Chunliang Li", "orcid": "0000-0002-5938-5510" }, { "affs": [ 0 ], "name": "Yongqiang Feng", "orcid": "0000-0002-2320-5063" } ], "bibtex": "https://research.draconitic.com/paper/ezvywanfmxahe.bib", "cited_by": 0, "doi": "10.1126/sciadv.aeh9188", "fulltext_url": "https://europepmc.org/articles/PMC13715726", "id": "ezvywanfmxahe", "issns": [ "2375-2548" ], "landing_url": "https://www.science.org/doi/abs/10.1126/sciadv.aeh9188", "language": "eng", "licence": "CC-BY-NC", "licence_label": "CC BY-NC", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Biomedicine and Life Sciences" ], [ "heading", "Diseases and Disorders" ], [ "heading", "Immunology" ], [ "heading", "Research Article" ], [ "heading", "SciAdv r-articles" ], [ "openalex", "2403|T-cell and B-cell Immunology" ] ], "openalex": "W7224132697", "pdf_url": "https://europepmc.org/articles/PMC13715726?pdf=render", "pmcid": "PMC13715726", "pmid": "42950054", "published": "2026-10-28", "publisher": "American Association for the Advancement of Science (AAAS)", "ris": "https://research.draconitic.com/paper/ezvywanfmxahe.ris", "sources": [ { "first_seen": "2026-10-30T12:17:16Z", "native_id": "10.1126/sciadv.aeh9188", "source": "feed-science", "url": "https://www.science.org/doi/abs/10.1126/sciadv.aeh9188" }, { "first_seen": "2026-10-30T12:17:41Z", "native_id": "10.1126/sciadv.aeh9188", "source": "crossref", "url": "https://www.science.org/doi/10.1126/sciadv.aeh9188" }, { "first_seen": "2026-10-31T00:20:33Z", "native_id": "MED:42950054", "source": "europepmc", "url": "https://europepmc.org/article/MED/42950054" }, { "first_seen": "2026-11-01T12:22:56Z", "native_id": "PMC13715726", "source": "pmc", "url": "https://doi.org/10.1126/sciadv.aeh9188" } ], "subjects": [ { "field": "biology", "origin": "heading:Immunology", "subfield": "immunology" } ], "title": "Wdr82-COMPASS coordinates Foxp3 and TCR signaling to sustain Treg cell control of microbiota-driven intestinal inflammation", "title_text": "Wdr82-COMPASS coordinates Foxp3 and TCR signaling to sustain Treg cell control of microbiota-driven intestinal inflammation", "type": "peer-reviewed", "updated_at": "2026-11-01T12:22:56Z", "url": "https://research.draconitic.com/paper/ezvywanfmxahe", "venue": "Science Advances", "versions": [] }