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

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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:
CreatorsEmailORCIDORCID Put Code
Wunderlich, Claudia M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ackermann, P. JustusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ostermann, Anna LenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Adams-Quack, PetraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vogt, Merly C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tran, My-LyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nikolajev, AlexeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waisman, AriUNSPECIFIEDorcid.org/0000-0003-4304-8234UNSPECIFIED
Garbers, ChristophUNSPECIFIEDorcid.org/0000-0003-4939-6950UNSPECIFIED
Theurich, SebastianUNSPECIFIEDorcid.org/0000-0001-5706-8258UNSPECIFIED
Mauer, JanUNSPECIFIEDorcid.org/0000-0002-0189-5876UNSPECIFIED
Hoevelmeyer, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wunderlich, F. ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
DELTA T-CELLS; TUMOR-ASSOCIATED MACROPHAGES; NECROSIS-FACTOR-ALPHA; INSULIN-RESISTANCE; B-CELLS; INFLAMMATORY PROTEIN-3-ALPHA/CCL20; SIGNALING PREVENTS; COLORECTAL-CANCER; ACTIVATION; IL-6Multiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/18906

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