» Articles » PMID: 28586167

Card9-dependent IL-1β Regulates IL-22 Production from Group 3 Innate Lymphoid Cells and Promotes Colitis-associated Cancer

Overview
Journal Eur J Immunol
Date 2017 Jun 7
PMID 28586167
Citations 38
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

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.


Identification of a genetic region linked to tolerance to MRSA infection using Collaborative Cross mice.

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.


References
1.
Taupin D, Podolsky D . Trefoil factors: initiators of mucosal healing. Nat Rev Mol Cell Biol. 2003; 4(9):721-32. DOI: 10.1038/nrm1203. View

2.
Hara H, Saito T . CARD9 versus CARMA1 in innate and adaptive immunity. Trends Immunol. 2009; 30(5):234-42. DOI: 10.1016/j.it.2009.03.002. View

3.
Salcedo R, Worschech A, Cardone M, Jones Y, Gyulai Z, Dai R . MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18. J Exp Med. 2010; 207(8):1625-36. PMC: 2916129. DOI: 10.1084/jem.20100199. View

4.
Iliev I, Funari V, Taylor K, Nguyen Q, Reyes C, Strom S . Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science. 2012; 336(6086):1314-7. PMC: 3432565. DOI: 10.1126/science.1221789. View

5.
Hoyler T, Klose C, Souabni A, Turqueti-Neves A, Pfeifer D, Rawlins E . The transcription factor GATA-3 controls cell fate and maintenance of type 2 innate lymphoid cells. Immunity. 2012; 37(4):634-48. PMC: 3662874. DOI: 10.1016/j.immuni.2012.06.020. View