TY  - JOUR
A1  - Richter, Cornelia
A1  - Herrero San Juan, Martina
A1  - Weigmann, Benno
A1  - Bergis, Dominik
A1  - Dauber, Katrin
A1  - Muders, Michael Helmut
A1  - Baretton, Gustavo Bruno
A1  - Pfeilschifter, Josef
A1  - Bönig, Halvard-Björn
A1  - Brenner, Sebastian
A1  - Radeke, Heinfried H.
T1  - Defective IL-23/IL-17 axis protects p47phox−/− mice from colon cancer
T2  - Frontiers in immunology
N2  - In the colon, a sophisticated balance between immune reaction and tolerance is absolutely required. Dysfunction may lead to pathologic phenotypes ranging from chronic inflammatory processes to cancer development. Two prominent modulators of colon inflammation are represented by the closely related cytokines interleukin (IL)-12 and IL-23, which initiate adaptive Th1 and Th17 immune responses, respectively. In this study, we investigated the impact of the NADPH oxidase protein p47phox, which negatively regulates IL-12 in dendritic cells, on colon cancer development in a colitis-associated colon cancer model. Initially, we found that IL-12−/− mice developed less severe colitis but are highly susceptible to colon cancer. By contrast, p47phox−/− mice showed lower tumor scores and fewer high grade tumors than wild-type (WT) littermates. Treatment with toll-like receptor 9 ligand CpG2216 significantly enhanced colitis in p47phox−/− mice, whereas tumor growth was simultaneously reduced. In tumor tissue of p47phox−/− mice, the IL-23/IL-17 axis was crucially hampered. IL-23p19 protein expression in tumor tissue correlated with tumor stage. Reconstitution of WT mice with IL-23p19−/− bone marrow protected these mice from colon cancer, whereas transplantation of WT hematopoiesis into IL-23p19−/− mice increased the susceptibility to tumor growth. Our study strengthens the divergent role of IL-12 and IL-23 in colon cancer development. With the characterization of p47phox as a novel modulator of both cytokines our investigation introduces a promising new target for antitumor strategies.
KW  - p47phox
KW  - DSS /AOM
KW  - IL -23
KW  - IL -17
KW  - chronic colitis
KW  - colon cancer
KW  - IL 23p19 knockout mouse
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/51776
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-517760
SN  - 1664-3224
N1  - Copyright: © 2017 Richter, Herrero San Juan, Weigmann, Bergis, Dauber, Muders, Baretton, Pfeilschifter, Bonig, Brenner and Radeke. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
VL  - 8
IS  - Art. 44
SP  - 1
EP  - 10
PB  - Frontiers Media
CY  - Lausanne
ER  -