title: A pathogenic role for T cell-derived IL-22BP in inflammatory bowel disease.
abstract: Intestinal inflammation can impair mucosal healing, thereby establishing a vicious cycle leading to chronic inflammatory bowel disease (IBD). However, the signaling networks driving chronic inflammation remain unclear. Here we report that CD4+T cells isolated from patients with IBD produce high levels of interleukin-22 binding protein (IL-22BP), the endogenous inhibitor of the tissue-protective cytokine IL-22. Using mouse models, we demonstrate that IBD development requires T cell-derived IL-22BP. Lastly, intestinal CD4+T cells isolated from IBD patients responsive to treatment with antibodies against tumor necrosis factor-α (anti-TNF-α), the most effective known IBD therapy, exhibited reduced amounts of IL-22BP expression but still expressed IL-22. Our findings suggest that anti-TNF-α therapy may act at least in part by suppressing IL-22BP and point toward a more specific potential therapy for IBD.
authors.affiliation: I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Penelope
authors.initials: P
authors.lastname: Pelczar
authors.affiliation: I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.|Institut für Medizinische Mikrobiologie und Hygiene, Obere Zahlbacherstraße 67, 55131 Mainz, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Witkowski
authors.affiliation: I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Laura Garcia
authors.initials: LG
authors.lastname: Perez
authors.affiliation: I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Kempski
authors.affiliation: I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Anna G
authors.initials: AG
authors.lastname: Hammel
authors.affiliation: I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Leonie
authors.initials: L
authors.lastname: Brockmann
authors.affiliation: I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Dörte
authors.initials: D
authors.lastname: Kleinschmidt
authors.affiliation: I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Wende
authors.affiliation: I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Cathleen
authors.initials: C
authors.lastname: Haueis
authors.affiliation: I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Bedke
authors.affiliation: Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Witkowski
authors.affiliation: Institut für Neuropathologie, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Krasemann
authors.affiliation: Institut für Pathologie, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Steurer
authors.affiliation: Section of Comparative Medicine, School of Medicine, Yale University, New Haven, CT 06520, USA.
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Booth
authors.affiliation: Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Busch
authors.affiliation: Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: König
authors.affiliation: Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Rauch
authors.affiliation: I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Benten
authors.affiliation: Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.affiliation: Klinik und Poliklinik für Interdisziplinäre Endoskopie, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rösch
authors.affiliation: I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Ansgar W
authors.initials: AW
authors.lastname: Lohse
authors.affiliation: Helmholtz-Zentrum für Infektionsforschung, 38124 Braunschweig, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Strowig
authors.affiliation: I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.|Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Gagliani
authors.affiliation: Howard Hughes Medical Institute and Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA. richard.flavell@yale.edu shuber@uke.de richard.flavell@yale.edu shuber@uke.de.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.affiliation: I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany. richard.flavell@yale.edu shuber@uke.de richard.flavell@yale.edu shuber@uke.de.
authors.forename: Samuel
authors.initials: S
authors.lastname: Huber
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D018928:Immunity, Mucosal; D007167:Immunotherapy; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000628:therapy; D007413:Intestinal Mucosa / Q000276:immunology*; D051379:Mice; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000906:Antibodies; D018123:Receptors, Interleukin; D014409:Tumor Necrosis Factor-alpha; C415369:interleukin-22 receptor