Format

Send to

Choose Destination
Science. 2016 Oct 21;354(6310):358-362.

A pathogenic role for T cell-derived IL-22BP in inflammatory bowel disease.

Author information

1
I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
2
Institut für Medizinische Mikrobiologie und Hygiene, Obere Zahlbacherstraße 67, 55131 Mainz, Germany.
3
Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
4
Institut für Neuropathologie, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
5
Institut für Pathologie, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
6
Section of Comparative Medicine, School of Medicine, Yale University, New Haven, CT 06520, USA.
7
Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
8
Klinik und Poliklinik für Interdisziplinäre Endoskopie, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
9
Helmholtz-Zentrum für Infektionsforschung, 38124 Braunschweig, Germany.
10
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.
11
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.

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.

PMID:
27846573
DOI:
10.1126/science.aah5903
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center