Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation
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 I...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-08-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716309858 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation Cell Reports |
| author_facet |
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 |
| author_sort |
Konrad Aden |
| title |
Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation |
| title_short |
Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation |
| title_full |
Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation |
| title_fullStr |
Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation |
| title_full_unstemmed |
Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal Inflammation |
| title_sort |
epithelial il-23r signaling licenses protective il-22 responses in intestinal inflammation |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2016-08-01 |
| description |
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. |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124716309858 |
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doaj-c7ad691214884543bd2eb9b5ed88874d2020-11-25T01:28:27ZengElsevierCell Reports2211-12472016-08-011682208221810.1016/j.celrep.2016.07.054Epithelial IL-23R Signaling Licenses Protective IL-22 Responses in Intestinal InflammationKonrad Aden0Ateequr Rehman1Maren Falk-Paulsen2Thomas Secher3Jan Kuiper4Florian Tran5Steffen Pfeuffer6Raheleh Sheibani-Tezerji7Alexandra Breuer8Anne Luzius9Marlene Jentzsch10Robert Häsler11Susanne Billmann-Born12Olga Will13Simone Lipinski14Richa Bharti15Timon Adolph16Juan L. Iovanna17Sarah L. Kempster18Richard S. Blumberg19Stefan Schreiber20Burkhard Becher21Mathias Chamaillard22Arthur Kaser23Philip Rosenstiel24Institute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyInstitute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyInstitute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyUniversity Toulouse, CNRS, Inserm, CHU Toulouse, UMR 1043-UMR 5282, Centre de Physiopathologie Toulouse Purpan, 31024 Toulouse, FranceInstitute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyInstitute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyInstitute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyInstitute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyInstitute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyInstitute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyInstitute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyInstitute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyInstitute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyInstitute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyInstitute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyInstitute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyDivision of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, England, UKAix-Marseille University, Institut Paoli-Calmettes, CNRS, Inserm, UMR 1068-UMR 7258, Centre de Recherche en Carcérologie de Marseille, 13273 Marseille, FranceDivision of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, England, UKGastroenterology Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USAInstitute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyInstitute of Experimental Immunology, University of Zurich, 8057 Zurich, SwitzerlandUniversity Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204–CIIL, Centre d’Infection et d’Immunité de Lille, 59000 Lille, FranceDivision of Gastroenterology and Hepatology, Department of Medicine, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, England, UKInstitute of Clinical Molecular Biology, Christian Albrechts University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyA 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.http://www.sciencedirect.com/science/article/pii/S2211124716309858 |