ArticleCell reports2020
An IL-27-Driven Transcriptional Network Identifies Regulators of IL-10 Expression across T Helper Cell Subsets.
Erratum issuedOpen access · goldAbstract read
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Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 58 papers.
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58citing papers in PubMed
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58 citing papers in PubMed, 85 citations in OpenAlex.
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- Pbx1 as a regulator of T-cell fate in autoimmunity.Frontiers in immunology · 2026Review
- T-cell lymphoma-associated STAT3 variants impose a type 1 regulatory-like phenotype.Frontiers in immunology · 2026Article
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- ICOS regulates IL-10 production in group 2 innate lymphoid cells via cholesterol and cortisol biosynthesis.The Journal of clinical investigation · 2025Article
- Targeting Impaired Type I Interferon-IL-27 Signaling Rescues T Regulatory Cell Suppressive Function in Relapsing-Remitting Multiple Sclerosis.bioRxiv : the preprint server for biology · 2025Article
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- BLIMP1 negatively regulates IL-2 signaling in T cells.Science advances · 2025Article
- Human MAIT cell response profiles biased toward IL-17 or IL-10 are distinct effector states directed by the cytokine milieu.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Maf expression in B cells restricts reactive plasmablast and germinal center B cell expansion.Nature communications · 2024Article
- IL-27/Blimp-1 axis regulates the differentiation and function of Tim-3+ Tregs during early pregnancy.JCI insight · 2024Article
- BACH2 regulates diversification of regulatory and proinflammatory chromatin states in TNature immunology · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
25 authors at 6 institutions in 6 countries.
Huiyuan ZhangEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
Asaf MadiEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: asafmadi@tauex.tau.ac.il.
Nir YosefEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; Department of Electrical Engineering and Computer Science and Center for Computational Biology, University of California, Berkeley, CA, USA.
Norio ChiharaEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; Division of Neurology, Kobe University Graduate School of Medicine, Kobe, Japan.
Amit AwasthiEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; Center for Human Microbial Ecology, Translational Health Science and Technology Institute(an autonomous institute of the Department of Biotechnology, Government of India), NCR Biotech Science Cluster, Faridabad, India.
Caroline PotEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; Laboratories of Neuroimmunology, Division of Neurology and Neuroscience Research Center, Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland.
Conner LambdenEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Amitabh SrivastavaDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Patrick R BurkettEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; Biogen, 300 Binney St., Cambridge, MA, USA.
Jackson NymanEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Elena ChristianEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Yasaman EtminanEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
Annika LeeEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
Helene StrohEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
Junrong XiaEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
Katarzyna KarwaczEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY, USA.
Pratiksha I ThakoreKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nandini AcharyaEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
Alexandra SchnellEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
Chao WangEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
Lionel ApetohEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; INSERM, U1231, Dijon, France.
Orit Rozenblatt-RosenKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Ana C AndersonEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
Aviv RegevKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Department of Biology, Koch Institute and Ludwig Center, Massachusetts Institute of Technology, Cambridge, MA, USA; Genentech, 1 DNA Way, South San Francisco, CA, USA. Electronic address: aregev@broadinstitute.org.
Vijay K KuchrooEvergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: vkuchroo@evergrande.hms.harvard.edu.
Harvard University · USBrigham and Women's Hospital · USBroad Institute · USInserm · FRTranslational Health Science and Technology Institute · INUniversity of California, Berkeley · US
Funding
Role of Negative Costimulation in Regulation of AutoimmunityP01AI039671 · NIAID · YALE UNIVERSITY · PI David A. Hafler · 1996 to 2026
$51.7MTransgenic/KnockoutP01AI056299 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI SHARPE, ARLENE H. · 2003 to 2023
$42.5MTransgenic / Knock-out mouse coreP01AI073748 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI BEHAR, SAMUEL M · 2008 to 2019
$17.1MProject 2: Genes required for dendritic cell responses to pathogens and T cellsU19AI133524 · NIAID · HARVARD MEDICAL SCHOOL · PI SHARPE, ARLENE H. · 2017 to 2021
$12.3MTranslational Core (Expression Core)P01AI129880 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ROTHSTEIN, DAVID M · 2018 to 2022
$9.4MT CELL RESPONSE TO MYELIN PROTEOLIPID PROTEINR01NS030843 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI KUCHROO, VIJAY K. · 1998 to 2019
$4.1MRole of Tim-3:Bat-3 pathway in inducing tolerogenic DCs and peripheral toleranceR01AI144166 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI VIJAY K. KUCHROO · 2020 to 2026
$3.2MSteroid hormone regulation of immune responsesR01CA229400 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ANDERSON, ANA C · 2018 to 2022
$1.9MEuropean Research Council 677251NCI NIH HHS R01 CA229400NIAID NIH HHS P01 AI039671NIAID NIH HHS P01 AI056299NIAID NIH HHS P01 AI073748NIAID NIH HHS P01 AI129880NIAID NIH HHS R01 AI144166NIAID NIH HHS U19 AI133524NINDS NIH HHS R01 NS030843
Abstract
Interleukin-27 (IL-27) is an immunoregulatory cytokine that suppresses inflammation through multiple mechanisms, including induction of IL-10, but the transcriptional network mediating its diverse functions remains unclear. Combining temporal RNA profiling with computational algorithms, we predict 79 transcription factors induced by IL-27 in T cells. We validate 11 known and discover 5 positive (Cebpb, Fosl2, Tbx21, Hlx, and Atf3) and 2 negative (Irf9 and Irf8) Il10 regulators, generating an experimentally refined regulatory network for Il10. We report two central regulators, Prdm1 and Maf, that cooperatively drive the expression of signature genes induced by IL-27 in type 1 regulatory T cells, mediate IL-10 expression in all T helper cells, and determine the regulatory phenotype of colonic Foxp3
Indexed as
AnimalsGene Regulatory NetworksHumansInterleukin-10Interleukin-27MiceMice, KnockoutTh1 CellsInterleukin-10Interleukin-27colitisIL-10IL-27MafPrdm1T helper cellsTr1transcriptional networkTreg
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