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PMID: 21559338 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Tumor-associated macrophages recruit CCR6+ regulatory T cells and promote the development of colorectal cancer via enhancing CCL20 production in mice.

PloS one ·Vol. 6 ·No. 4 ·2011-04-29 ·Pages e19495

Liu J, Zhang N, Li Q, Zhang W, Ke F, Leng Q, Wang H, Chen J, Wang H

Abstract

Tumor-associated macrophages (TAMs) remodel the colorectal cancer (CRC) microenvironment. Yet, findings on the role of TAMs in CRC seem to be contradictory compared with other cancers. FoxP3(+) regulatory T (Treg)-cells dominantly infiltrate CRC. However, the underlying molecular mechanism in which TAMs may contribute to the trafficking of Treg-cells to the tumor mass remains unknown. CRC was either induced by N-methyl-N-nitrosourea (MNU) and H. pylori or established by subcutaneous injection of mouse colorectal tumor cell line (CMT93) in mice. CMT93 cells were co-cultured with primary macrophages in a transwell apparatus. Recruitment of FoxP3 green fluorescence protein positive (FoxP3(GFP+)) Treg-cells was assessed using the IVIS Imaging System or immunofluorescence staining. A role for macrophages in trafficking of Treg-cells and in the development of CRC was investigated in CD11b diphtheria toxin receptor (CD11b-DTR) transgenic C57BL/6J mice in which macrophages can be selectively depleted. Treg-cells remarkably infiltrated solid tumor, and predominantly expressed the homing chemokine receptor (CCR) 6 in the induced CRC model. Both CMT93 cancer cells and macrophages produced a large amount of CCL20, the sole ligand of CCR6 in vitro and in vivo. Injection of recombinant mouse CCL20 into tumor sites promoted its development with a marked recruitment of Treg-cells in the graft CRC model. Conditional macrophage ablation decreased CCL20 levels, blocked Treg-cell recruitment and inhibited tumor growth in CD11b-DTR mice grafted with CMT93. TAMs recruit CCR6(+) Treg-cells to tumor mass and promote its development via enhancing the production of CCL20 in a CRC mouse model.

MeSH Terms
Animals CD11b Antigen/biosynthesis Chemokine CCL20/metabolism Female Forkhead Transcription Factors/biosynthesis Green Fluorescent Proteins/metabolism Helicobacter pylori/metabolism Lymphocytes, Tumor-Infiltrating/cytology Macrophages/cytology,metabolism Methylnitrosourea/pharmacology Mice Mice, Inbred C57BL Mice, Transgenic Microscopy, Fluorescence/methods Receptors, CCR6/biosynthesis T-Lymphocytes, Regulatory/cytology
Chemicals
CCL20 protein, mouse CCR6 protein, mouse CD11b Antigen Chemokine CCL20 Forkhead Transcription Factors Foxp3 protein, mouse Receptors, CCR6 Green Fluorescent Proteins Methylnitrosourea
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Liu Jinlin
Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Zhang Ning
Li Qun
Zhang Weiwei
Ke Fang
Leng Qibin
Wang Hong
Chen Jinfei
Wang Honglin
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0019495
Published
2011-04-29
Epub
2011-00-29
Pages
e19495
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3084880
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0019495 PMC Full Text View journal details
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