Card9-dependent IL-1β regulates IL-22 production from group 3 innate lymphoid cells and promotes colitis-associated cancer

• Verfasst von: Bergmann, Hanna [VerfasserIn]
• Verfasst von: Roth, Susanne [VerfasserIn]
• Titel: Card9-dependent IL-1β regulates IL-22 production from group 3 innate lymphoid cells and promotes colitis-associated cancer
• Verf.angabe: Hanna Bergmann, Susanne Roth, Konstanze Pechloff, Elina A. Kiss, Sabine Kuhn, Mathias Heikenwälder, Andreas Diefenbach, Florian R. Greten, Jürgen Ruland
• Umfang: 12 S.
• Fussnoten: Gesehen am 11.05.2018
• Titel Quelle: Enthalten in: European journal of immunology
• Jahr Quelle: 2017
• Band/Heft Quelle: 47(2017), 8, S. 1342-1353
• ISSN Quelle: 1521-4141
• DOI: doi:10.1002/eji.201646765
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1574993135

Abstract

Inflammatory bowel diseases (IBD) are key risk factors for the development of colorectal cancer, but the mechanisms that link intestinal inflammation with carcinogenesis are insufficiently understood. Card9 is a myeloid cell-specific signaling protein that regulates inflammatory responses downstream of various pattern recognition receptors and which cooperates with the inflammasomes for IL-1β production. Because polymorphisms in Card9 were recurrently associated with human IBD, we investigated the function of Card9 in a colitis-associated cancer (CAC) model. Card9−/− mice develop smaller, less proliferative and less dysplastic tumors compared to their littermates and in the regenerating mucosa we detected dramatically impaired IL-1β generation and defective IL-1β controlled IL-22 production from group 3 innate lymphoid cells. Consistent with the key role of immune-derived IL-22 in activating STAT3 signaling during normal and pathological intestinal epithelial cell (IEC) proliferation, Card9−/− mice also exhibit impaired tumor cell intrinsic STAT3 activation. Our results imply a Card9-controlled, ILC3-mediated mechanism regulating healthy and malignant IEC proliferation and demonstrates a role of Card9-mediated innate immunity in inflammation-associated carcinogenesis.