RGD Reference Report - CCR6 selectively promotes monocyte mediated inflammation and atherogenesis in mice. - Rat Genome Database

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CCR6 selectively promotes monocyte mediated inflammation and atherogenesis in mice.

Authors: Manthey, HD  Cochain, C  Barnsteiner, S  Karshovska, E  Pelisek, J  Koch, M  Chaudhari, SM  Busch, M  Eckstein, HH  Weber, C  Koenen, RR  Zernecke, A 
Citation: Manthey HD, etal., Thromb Haemost. 2013 Nov 27;110(6):1267-77. doi: 10.1160/TH13-01-0017. Epub 2013 Oct 10.
RGD ID: 7483610
Pubmed: PMID:24114205   (View Abstract at PubMed)
DOI: DOI:10.1160/TH13-01-0017   (Journal Full-text)

The chemokine receptor CCR6 is expressed by various cell subsets implicated in atherogenesis, such as monocytes, Th17 and regulatory T cells. In order to further define the role of CCR6 in atherosclerosis, CCR6-deficient (Ccr6-/-) mice were crossed with low-density lipoprotein receptor-deficient (Ldlr-/-) mice to generate atherosclerosis-prone mice deficient in CCR6. Compared to Ldlr-/- controls, atherosclerotic burden in the aortic sinus and aorta were reduced in Ccr6-/-Ldlr-/- mice fed a high fat diet, associated with a profound depression in lesional macrophage accumulation. Local and systemic distributions of T cells, including frequencies of Th1, Th17 and regulatory T cells were unaltered. In contrast, circulating counts of both Gr-1high and Gr1low monocytes were reduced in Ccr6-/-Ldlr-/- mice. Moreover, CCR6 was revealed to promote monocyte adhesion to inflamed endothelium in vitro and leukocyte adhesion to carotid arteries in vivo. Finally, CCR6 selectively recruited monocytes but not T cells in an acute inflammatory air pouch model. We here show that CCR6 functions on multiple levels and regulates the mobilisation, adhesion and recruitment of monocytes/macrophages to the inflamed vessel, thereby promoting atherosclerosis, but is dispensable for hypercholesterolaemia-associated adaptive immune priming. Targeting CCR6 or its ligand CCL20 may therefore be a promising therapeutic strategy to alleviate atherosclerosis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CCR6Humanatherosclerosis  ISOCcr6 (Mus musculus) RGD 
Ccr6Ratatherosclerosis  ISOCcr6 (Mus musculus) RGD 
Ccr6Mouseatherosclerosis  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccr6  (C-C motif chemokine receptor 6)

Genes (Mus musculus)
Ccr6  (C-C motif chemokine receptor 6)

Genes (Homo sapiens)
CCR6  (C-C motif chemokine receptor 6)


Additional Information