Journal article

Transcriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis

  • Hu, Dan Ann Romney Center for Neurologic Diseases and Evergrande Center for Immunologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
  • Notarbartolo, Samuele Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Croonenborghs, Tom Program in Translational NeuroPsychiatric Genomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA - KU Leuven Technology Campus Geel, AdvISe, Kleinhoefstraat 4, 2440 Geel, Belgium - Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA
  • Patel, Bonny Ann Romney Center for Neurologic Diseases and Evergrande Center for Immunologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
  • Cialic, Ron Ann Romney Center for Neurologic Diseases and Evergrande Center for Immunologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
  • Yang, Tun-Hsiang Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
  • Aschenbrenner, Dominik Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Translational Gastroenterology Unit, NDM Experimental Medicine, University of Oxford, Headington, OX3 9DU, UK
  • Andersson, Karin M. Department of Rheumatology and Inflammation Research, Sahlgrenska University Hospital, Gothenburg University, Box 480, 405 30 Gothenburg, Sweden
  • Gattorno, Marco Second Division of Pediatrics, G. Gaslini Scientific Institute, Largo Gerolamo Gaslini, 5, 16100 Genova(GE), Italy
  • Pham, Minh Ann Romney Center for Neurologic Diseases and Evergrande Center for Immunologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
  • Kivisakk, Pia Ann Romney Center for Neurologic Diseases and Evergrande Center for Immunologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
  • Pierre, Isabelle V. Ann Romney Center for Neurologic Diseases and Evergrande Center for Immunologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
  • Lee, Youjin Ann Romney Center for Neurologic Diseases and Evergrande Center for Immunologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
  • Kiani, Karun Program in Translational NeuroPsychiatric Genomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
  • Bokarewa, Maria Department of Rheumatology and Inflammation Research, Sahlgrenska University Hospital, Gothenburg University, Box 480, 405 30 Gothenburg, Sweden
  • Tjon, Emily Ann Romney Center for Neurologic Diseases and Evergrande Center for Immunologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
  • Pochet, Nathalie Program in Translational NeuroPsychiatric Genomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
  • Sallusto, Federica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Institute of Microbiology, ETH Zurich, Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, Switzerland
  • Kuchroo, Vijay K. Ann Romney Center for Neurologic Diseases and Evergrande Center for Immunologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
  • Weiner, Howard L. Ann Romney Center for Neurologic Diseases and Evergrande Center for Immunologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
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    17.11.2017
Published in:
  • Nature communications. - 2017, vol. 8, p. 1600
English We have previously reported the molecular signature of murine pathogenic TH17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. Here we show that human peripheral blood IFN-γ+IL-17+ (TH1/17) and IFN-γ−IL-17+ (TH17) CD4+ T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared to TH17 cells, TH1/17 cells have gene signatures with marked similarity to mouse pathogenic TH17 cells. Assessing 15 representative signature genes in patients with multiple sclerosis, we find that TH1/17 cells have elevated expression of CXCR3 and reduced expression of IFNG, CCL3, CLL4, GZMB, and IL10 compared to healthy controls. Moreover, higher expression of IL10 in TH17 cells is found in clinically stable vs. active patients. Our results define the molecular signature of human pro-inflammatory TH17 cells, which can be used to both identify pathogenic TH17 cells and to measure the effect of treatment on TH17 cells in human autoimmune diseases.
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  • English
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Medicine
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https://susi.usi.ch/usi/documents/319022
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