Cell Reports (Aug 2016)
Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation
- Konrad Aden,
- Ateequr Rehman,
- Maren Falk-Paulsen,
- Thomas Secher,
- Jan Kuiper,
- Florian Tran,
- Steffen Pfeuffer,
- Raheleh Sheibani-Tezerji,
- Alexandra Breuer,
- Anne Luzius,
- Marlene Jentzsch,
- Robert Häsler,
- Susanne Billmann-Born,
- Olga Will,
- Simone Lipinski,
- Richa Bharti,
- Timon Adolph,
- Juan L. Iovanna,
- Sarah L. Kempster,
- Richard S. Blumberg,
- Stefan Schreiber,
- Burkhard Becher,
- Mathias Chamaillard,
- Arthur Kaser,
- Philip Rosenstiel
Affiliations
- Konrad Aden
- Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
- Ateequr Rehman
- Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
- Maren Falk-Paulsen
- Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
- Thomas Secher
- University Toulouse, CNRS, Inserm, CHU Toulouse, UMR 1043-UMR 5282, Centre de Physiopathologie Toulouse Purpan, 31024 Toulouse, France
- Jan Kuiper
- Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
- Florian Tran
- Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
- Steffen Pfeuffer
- Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
- Raheleh Sheibani-Tezerji
- Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
- Alexandra Breuer
- Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
- Anne Luzius
- Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
- Marlene Jentzsch
- Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
- Robert Häsler
- Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
- Susanne Billmann-Born
- Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
- Olga Will
- Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
- Simone Lipinski
- Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
- Richa Bharti
- Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
- Timon Adolph
- Division of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, England, UK
- Juan L. Iovanna
- Aix-Marseille University, Institut Paoli-Calmettes, CNRS, Inserm, UMR 1068-UMR 7258, Centre de Recherche en Carcérologie de Marseille, 13273 Marseille, France
- Sarah L. Kempster
- Division of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, England, UK
- Richard S. Blumberg
- Gastroenterology Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- Stefan Schreiber
- Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
- Burkhard Becher
- Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland
- Mathias Chamaillard
- University Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204–CIIL, Centre d’Infection et d’Immunité de Lille, 59000 Lille, France
- Arthur Kaser
- Division of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, England, UK
- Philip Rosenstiel
- Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
- DOI
- https://doi.org/10.1016/j.celrep.2016.07.054
- Journal volume & issue
-
Vol. 16,
no. 8
pp. 2208 – 2218
Abstract
A plethora of functional and genetic studies have suggested a key role for the IL-23 pathway in chronic intestinal inflammation. Currently, pathogenic actions of IL-23 have been ascribed to specific effects on immune cells. Herein, we unveil a protective role of IL-23R signaling. Mice deficient in IL-23R expression in intestinal epithelial cells (Il23RΔIEC) have reduced Reg3b expression, show a disturbed colonic microflora with an expansion of flagellated bacteria, and succumb to DSS colitis. Surprisingly, Il23RΔIEC mice show impaired mucosal IL-22 induction in response to IL-23. αThy-1 treatment significantly deteriorates colitis in Il23RΔIEC animals, which can be rescued by IL-22 application. Importantly, exogenous Reg3b administration rescues DSS-treated Il23RΔIEC mice by recruiting neutrophils as IL-22-producing cells, thereby restoring mucosal IL-22 levels. The study identifies a critical barrier-protective immune pathway that originates from, and is orchestrated by, IL-23R signaling in intestinal epithelial cells.
