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An IL-27-Driven Transcriptional Network Identifies Regulators of IL-10 Expression across T Helper Cell Subsets.
Zhang, Huiyuan; Madi, Asaf; Yosef, Nir; Chihara, Norio; Awasthi, Amit; Pot, Caroline; Lambden, Conner; Srivastava, Amitabh; Burkett, Patrick R; Nyman, Jackson; Christian, Elena; Etminan, Yasaman; Lee, Annika; Stroh, Helene; Xia, Junrong; Karwacz, Katarzyna; Thakore, Pratiksha I; Acharya, Nandini; Schnell, Alexandra; Wang, Chao; Apetoh, Lionel; Rozenblatt-Rosen, Orit; Anderson, Ana C; Regev, Aviv; Kuchroo, Vijay K.
Afiliação
  • Zhang H; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
  • Madi A; Evergrande 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
  • Yosef N; Evergrande 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,
  • Chihara N; Evergrande 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.
  • Awasthi A; Evergrande 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 B
  • Pot C; Evergrande 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
  • Lambden C; Evergrande 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.
  • Srivastava A; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
  • Burkett PR; Evergrande 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.
  • Nyman J; Evergrande 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.
  • Christian E; Evergrande 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.
  • Etminan Y; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
  • Lee A; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
  • Stroh H; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
  • Xia J; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
  • Karwacz K; Evergrande 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.
  • Thakore PI; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Acharya N; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
  • Schnell A; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
  • Wang C; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
  • Apetoh L; Evergrande 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.
  • Rozenblatt-Rosen O; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Anderson AC; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
  • Regev A; Klarman 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 addres
  • Kuchroo VK; Evergrande 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.ed
Cell Rep ; 33(8): 108433, 2020 11 24.
Article em En | MEDLINE | ID: mdl-33238123
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+ regulatory T cells. Prdm1/Maf double-knockout mice develop spontaneous colitis, phenocopying ll10-deficient mice. Our work provides insights into IL-27-driven transcriptional networks and identifies two shared Il10 regulators that orchestrate immunoregulatory programs across T helper cell subsets.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interleucina-10 / Células Th1 / Redes Reguladoras de Genes / Interleucina-27 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interleucina-10 / Células Th1 / Redes Reguladoras de Genes / Interleucina-27 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos