Wunderlich, Claudia M., Ackermann, P. Justus, Ostermann, Anna Lena, Adams-Quack, Petra, Vogt, Merly C., Tran, My-Ly, Nikolajev, Alexei, Waisman, Ari ORCID: 0000-0003-4304-8234, Garbers, Christoph
ORCID: 0000-0003-4939-6950, Theurich, Sebastian
ORCID: 0000-0001-5706-8258, Mauer, Jan
ORCID: 0000-0002-0189-5876, Hoevelmeyer, Nadine and Wunderlich, F. Thomas
(2018).
Obesity exacerbates colitis-associated cancer via IL-6-regulated macrophage polarisation and CCL-20/CCR-6-mediated lymphocyte recruitment.
Nat. Commun., 9.
LONDON:
NATURE PUBLISHING GROUP.
ISSN 2041-1723
Abstract
Colorectal cancer (CRC) is one of the most lethal cancers worldwide in which the vast majority of cases exhibit little genetic risk but are associated with a sedentary lifestyle and obesity. Although the mechanisms underlying CRC and colitis-associated colorectal cancer (CAC) remain unclear, we hypothesised that obesity-induced inflammation predisposes to CAC development. Here, we show that diet-induced obesity accelerates chemically-induced CAC in mice via increased inflammation and immune cell recruitment. Obesity-induced interleukin-6 (IL-6) shifts macrophage polarisation towards tumour-promoting macrophages that produce the chemokine CC-chemokine-ligand-20 (CCL-20) in the CAC microenvironment. CCL-20 promotes CAC progression by recruiting CC-chemokine-receptor-6 (CCR-6)expressing B cells and gamma delta T cells via chemotaxis. Compromised cell recruitment as well as inhibition of B and gamma delta T cells protects against CAC progression. Collectively, our data reveal a function for IL-6 in the CAC microenvironment via lymphocyte recruitment through the CCL-20/CCR-6 axis, thereby implicating a potential therapeutic intervention for human patients.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Creators: |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
URN: | urn:nbn:de:hbz:38-189062 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
DOI: | 10.1038/s41467-018-03773-0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Nat. Commun. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Volume: | 9 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Date: | 2018 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Publisher: | NATURE PUBLISHING GROUP | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Place of Publication: | LONDON | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ISSN: | 2041-1723 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Uncontrolled Keywords: |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refereed: | Yes | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/18906 |
Downloads
Downloads per month over past year
Altmetric
Export
Actions (login required)
![]() |
View Item |