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

Hu, Dan; Notarbartolo, Samuele; Croonenborghs, Tom; Patel, Bonny; Cialic, Ron; Yang, Tun-Hsiang; Aschenbrenner, Dominik; Andersson, Karin M.; Gattorno, Marco; Pham, Minh; Kivisakk, Pia; Pierre, Isabelle V.; Lee, Youjin; Kiani, Karun; Bokarewa, Maria; Tjon, Emily; Pochet, Nathalie; Sallusto, Federica; Kuchroo, Vijay K.; Weiner, Howard L.

doi:10.1038/s41467-017-01571-8

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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

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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