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

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...

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Hauptverfasser: Bergmann, Hanna (VerfasserIn) , Roth, Susanne (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 06 June 2017
In: European journal of immunology
Year: 2017, Jahrgang: 47, Heft: 8, Pages: 1342-1353
ISSN:1521-4141
DOI:10.1002/eji.201646765
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1002/eji.201646765
Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/eji.201646765
Volltext
Verfasserangaben:Hanna Bergmann, Susanne Roth, Konstanze Pechloff, Elina A. Kiss, Sabine Kuhn, Mathias Heikenwälder, Andreas Diefenbach, Florian R. Greten, Jürgen Ruland
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 11.05.2018
Beschreibung:Online Resource
ISSN:1521-4141
DOI:10.1002/eji.201646765

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