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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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
06 June 2017
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| In: |
European journal of immunology
Year: 2017, Volume: 47, Issue: 8, Pages: 1342-1353 |
| ISSN: | 1521-4141 |
| DOI: | 10.1002/eji.201646765 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1002/eji.201646765 Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/eji.201646765 
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| Author Notes: | Hanna Bergmann, Susanne Roth, Konstanze Pechloff, Elina A. Kiss, Sabine Kuhn, Mathias Heikenwälder, Andreas Diefenbach, Florian R. Greten, Jürgen Ruland |
| Summary: | 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. |
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| Item Description: | Gesehen am 11.05.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1521-4141 |
| DOI: | 10.1002/eji.201646765 |