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Functional studies of T reg cells in vitro have defined multiple suppression mechanisms, and studies of T reg\u2013deficient humans and mice have made clear the important role that these cells play in preventing autoimmunity. However, many questions remain about how T reg cells act in vivo. Specifically, it is not clear which suppression mechanisms are most important, where T reg cells act, and how they get there. To begin to address these issues, we sought to identify T reg cells in zebrafish, a model system that provides unparalleled advantages in live-cell imaging and high-throughput genetic analyses. Using a FOXP3 orthologue as a marker, we identified CD4-enriched, mature T lymphocytes with properties of T reg cells. Zebrafish mutant for foxp3a displayed excess T lymphocytes, splenomegaly, and a profound inflammatory phenotype that was suppressed by genetic ablation of lymphocytes. This study identifies T reg\u2013like cells in zebrafish, providing both a model to study the normal functions of these cells in vivo and mutants to explore the consequences of their loss.<\/jats:p>","DOI":"10.1084\/jem.20162084","type":"journal-article","created":{"date-parts":[[2017,10,24]],"date-time":"2017-10-24T10:35:39Z","timestamp":1508841339000},"page":"3519-3530","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":73,"title":["Identification and characterization of T reg\u2013like cells in zebrafish"],"prefix":"10.1084","volume":"214","author":[{"given":"Melissa","family":"Kasheta","sequence":"first","affiliation":[{"name":"Program in Molecular Medicine and Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corrie A.","family":"Painter","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine and Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finola E.","family":"Moore","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA 2"},{"name":"Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 3"},{"name":"Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 4"},{"name":"Harvard Stem Cell Institute, Cambridge, MA 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riadh","family":"Lobbardi","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA 2"},{"name":"Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 3"},{"name":"Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 4"},{"name":"Harvard Stem Cell Institute, Cambridge, MA 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alysia","family":"Bryll","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine and Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6256-7120","authenticated-orcid":true,"given":"Eli","family":"Freiman","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine and Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Stachura","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, California State University, Chico, CA 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlin B.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yariv","family":"Houvras","sequence":"additional","affiliation":[{"name":"Departments of Surgery and Medicine, Weill Cornell Medical College, New York, NY 8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6664-8318","authenticated-orcid":true,"given":"David M.","family":"Langenau","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA 2"},{"name":"Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 3"},{"name":"Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 4"},{"name":"Harvard Stem Cell Institute, Cambridge, MA 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7188-7580","authenticated-orcid":true,"given":"Craig J.","family":"Ceol","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine and Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2017,10,24]]},"reference":[{"key":"2023072603472504200_bib1","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1016\/j.cell.2017.05.002","article-title":"Regulatory T cells in skin facilitate epithelial stem cell differentiation","volume":"169","author":"Ali","year":"2017","journal-title":"Cell."},{"key":"2023072603472504200_bib2","doi-asserted-by":"publisher","first-page":"113","DOI":"10.3389\/fimmu.2012.00113","article-title":"Comparative genomics reveals key gain-of-function events in Foxp3 during regulatory T cell evolution","volume":"3","author":"Andersen","year":"2012","journal-title":"Front. 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