CCR6 (C-C motif chemokine receptor 6, gene ID 1235), encoding a seven transmembrane protein similar to G protein-coupled receptors, expressed on B-cells, immature dendritic cells (DC), T-cells (Th1, Th2, Th17, Treg), natural killer cells (NKT cells) and neutrophils. This chemokine receptor bind only one chemokine ligand CCL20. CCR6 has a key role in connection between immature DC an adaptive immunity. It is important for B-lineage maturation, antigen-driven B-cell differentiation, and regulate the migration and recruitment of dendritic cells and T cells during inflammatory and immunological responses. Pro-inflammatory Th17 cells also express CCR6 and its ligand CCL20. CCR6 influences their migration to sites of inflammation. Some Th17 cells migrate via chemokine gradient of CCL20 to inflammatory sites and themselves can express more CCL20 to bring in more Th17 cells and regulatory T-cells. This can lead to chronic inflammation. In some models, the lack of CCR6 leads to less severe autoimmune encephalomyelitis.
CCR6 signaling induced phosphorylation of Akt, mTOR, and STAT3 molecules in T cells. Akt/mTOR/STAT3 signaling inhibits the expression of Foxp3 and promotes the expression of RORγt and IL-17 molecules in the T cell.
The CCL20-CCR6 axis promotes cancer progression directly by enhancing migration and proliferation of cancer cells and indirectly by remodeling the tumor microenvironment through immune cell control.
mRNA expression analysis
Strain specific analysis of CCR6 gene expression in B-hCCR6 mice by RT-PCR. Mouse Ccr6 mRNA was detectable in splenocytes of wild-type mice (+/+). Human CCR6 mRNA was detectable only in homozygous B-hCCR6 mice (H/H) but not in wild-type mice.
Protein expression analysis
Strain specific CCR6 expression analysis in homozygous B-hCCR6 mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6 (+/+) and homozygous B-hCCR6 mice (H/H), and analyzed by flow cytometry with anti-CCR6 antibody. Mouse CCR6 was detectable in C57BL/6 mice. Human CCR6 was only detectable in homozygous B-hCCR6 mice but not in C57BL/6 mice.