title: TH9 cells that express the transcription factor PU.1 drive T cell-mediated colitis via IL-9 receptor signaling in intestinal epithelial cells.
abstract: The molecular checkpoints that drive inflammatory bowel diseases are incompletely understood. Here we found more T cells expressing the transcription factor PU.1 and interleukin 9 (IL-9) in patients with ulcerative colitis. In an animal model, citrine reporter mice had more IL-9-expressing mucosal T cells in experimental oxazolone-induced colitis. IL-9 deficiency suppressed acute and chronic colitis. Mice with PU.1 deficiency in T cells were protected from colitis, whereas treatment with antibody to IL-9 suppressed colitis. Functionally, IL-9 impaired intestinal barrier function and prevented mucosal wound healing in vivo. Thus, our findings suggest that the TH9 subset of helper T cells serves an important role in driving ulcerative colitis by regulating intestinal epithelial cells and that TH9 cells represent a likely target for the treatment of chronic intestinal inflammation.
authors.affiliation: Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research, Erlangen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Gerlach
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: YouYi
authors.initials: Y
authors.lastname: Hwang
authors.affiliation: Institute of Molecular Medicine, University Medical Center Mainz, Mainz, Germany.
authors.forename: Alexej
authors.initials: A
authors.lastname: Nikolaev
authors.affiliation: Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research, Erlangen, Germany.
authors.forename: Raja
authors.initials: R
authors.lastname: Atreya
authors.affiliation: Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research, Erlangen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Dornhoff
authors.affiliation: Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research, Erlangen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Steiner
authors.affiliation: Institute of Pathology, Campus Bodensee, Friedrichshafen, Germany.
authors.forename: Hans-Anton
authors.initials: HA
authors.lastname: Lehr
authors.affiliation: Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research, Erlangen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wirtz
authors.affiliation: Institute of Pathology, Bayreuth Clinic, Bayreuth, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Vieth
authors.affiliation: Institute of Molecular Medicine, University Medical Center Mainz, Mainz, Germany.
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
authors.affiliation: Laboratory of Molecular Stem Cell Biology, University of Münster, Münster, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Rosenbauer
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Andrew N J
authors.initials: AN
authors.lastname: McKenzie
authors.affiliation: 1] Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research, Erlangen, Germany. [2].
authors.forename: Benno
authors.initials: B
authors.lastname: Weigmann
authors.affiliation: 1] Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research, Erlangen, Germany. [2].
authors.forename: Markus F
authors.initials: MF
authors.lastname: Neurath
mesh_terms: D000818:Animals; D062446:Claudin-2 / Q000235:genetics; D003092:Colitis / Q000209:etiology* / Q000276:immunology; D003093:Colitis, Ulcerative / Q000276:immunology; D006801:Humans; D016906:Interleukin-9 / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D053651:Receptors, Interleukin-9 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D015534:Trans-Activators / Q000502:physiology*; D014945:Wound Healing; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D062446:Claudin-2; D016906:Interleukin-9; D011518:Proto-Oncogene Proteins; D053651:Receptors, Interleukin-9; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1