Card9-dependent IL-1β Regulates IL-22 Production from Group 3 Innate Lymphoid Cells and Promotes Colitis-associated Cancer
Overview
Authors
Affiliations
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.
Tumor-related fungi and crosstalk with gut fungi in the tumor microenvironment.
Wang Y, Wang Y, Zhou Y, Feng Y, Sun T, Xu J Cancer Biol Med. 2024; 21(11).
PMID: 39601429 PMC: 11667784. DOI: 10.20892/j.issn.2095-3941.2024.0240.
Nagarajan A, Scoggin K, Adams L, Threadgill D, Andrews-Polymenis H PLoS Genet. 2024; 20(8):e1011378.
PMID: 39178306 PMC: 11407622. DOI: 10.1371/journal.pgen.1011378.
Fungi and tumors: The role of fungi in tumorigenesis (Review).
Cheng W, Li F, Gao Y, Yang R Int J Oncol. 2024; 64(5).
PMID: 38551162 PMC: 10997370. DOI: 10.3892/ijo.2024.5640.
Disease pathogenesis and barrier functions regulated by group 3 innate lymphoid cells.
Mori A, Ohno H, Satoh-Takayama N Semin Immunopathol. 2024; 45(4-6):509-519.
PMID: 38305897 DOI: 10.1007/s00281-024-01000-1.
ILC3: a case of conflicted identity.
Koprivica I, Stanisavljevic S, Micanovic D, Jevtic B, Stojanovic I, Miljkovic D Front Immunol. 2023; 14:1271699.
PMID: 37915588 PMC: 10616800. DOI: 10.3389/fimmu.2023.1271699.