Full Name: C-C Chemokine Receptor Type 6
Gene Symbol: CCR6
Aliases: CD196, BN-1, DWR
Chromosomal Location: 6q27
NCBI Gene ID: 1235
OMIM: 603526
Ensembl ID: ENSG00000112486
UniProt ID: P51671
Protein Length: 374 amino acids
CCR6 encodes a G protein-coupled receptor for CCL20 (MIP-3α/MIP-3a), also known as exodus-1 or LARC (Liver and Activation-Regulated Chemokine). CCR6 is expressed primarily on various immune cells and plays critical roles in Th17 cell trafficking, B cell migration, and dendritic cell positioning. Variants in CCR6 have been implicated in Multiple Sclerosis, Parkinson's Disease, Amyotrophic Lateral Sclerosis, and various autoimmune conditions including inflammatory bowel disease, rheumatoid arthritis, and psoriasis[ccr62019].
In the nervous system, CCR6 is primarily expressed on infiltrating immune cells rather than neurons or glia, making it a key regulator of immune-mediated neuroinflammation. The CCL20-CCR6 axis serves as a critical bridge between peripheral immunity and central nervous system pathology.
The CCR6 gene spans approximately 4.5 kb on chromosome 6q27 and consists of 4 exons. The gene encodes a 374-amino acid GPCR with the characteristic seven transmembrane domain architecture.
CCR6 contains:
- N-terminal extracellular domain: Ligand binding
- Seven transmembrane domains: GPCR core
- Three extracellular loops: Ligand interaction
- Three intracellular loops: Signal transduction
- C-terminal intracellular tail: G protein coupling and desensitization
¶ Ligand-Receptor Interaction
CCR6 binds exclusively to CCL20, a chemokine produced by:
- Astrocytes in the CNS
- Epithelial cells
- Dendritic cells
- Fibroblasts
- Activated T cells
CCR6 is a defining marker for Th17 cells[ccr62019]:
- Lineage specification: CCR6+ identifies IL-17-producing Th17 cells
- Tissue homing: Directs Th17 cells to sites of inflammation
- CNS infiltration: CCL20-CCR6 axis recruits autoreactive T cells to the CNS
- Autoimmunity: Th17 cells via CCR6 drive tissue damage in autoimmunity
CCR6 regulates B lymphocyte migration[ccr62019b]:
- Migration to secondary lymphoid organs
- Positioning in germinal centers
- Plasma cell differentiation
Dendritic cell CCR6[ccr62018]:
- Guides positioning in tissues
- Lymph node migration
- T cell priming
In mucosal tissues:
- Recruitment of immune cells to gut-associated lymphoid tissue
- Maintenance of intestinal immune homeostasis
- Defense against pathogens
CCR6 in T cell biology[ccr62018b]:
- Memory T cell maintenance
- Regulatory T cell trafficking
- γδ T cell function
CCR6 is a major player in MS pathogenesis[ccr62017]:
| Mechanism |
Evidence |
| Th17 recruitment |
CCR6+ Th17 cells infiltrate MS lesions |
| CNS homing |
CCL20 upregulated in MS brain |
| Animal models |
CCR6 knockout mice protected from EAE |
| Therapeutic |
Anti-CCR6 antibodies reduce disease |
CCR6 in PD[ccr62021]:
- Increased CCR6+ T cells in PD patients
- CCL20 elevated in substantia nigra
- Contribution to dopaminergic neuron loss
- Potential biomarker
CCR6 in ALS[ccr62024]:
- Elevated CCR6+ T cells in ALS patients
- CCR6+ T cells in spinal cord
- Contributes to motor neuron damage
CCR6 in IBD[ccr62016]:
- Critical for Th17 cell recruitment to intestines
- CCL20-CCR6 axis in Crohn's disease and ulcerative colitis
- Genetic association with IBD susceptibility
CCR6 in RA[ccr62022]:
- Th17 cells via CCR6 infiltrate joints
- CCL20 expressed in rheumatoid synovium
- Therapeutic targeting in development
CCR6 in psoriasis[ccr62015]:
- CCR6+ Th17 cells in skin lesions
- CCL20 upregulated in psoriatic skin
- Clinical trials of CCR6 antagonists
| Cell Type |
CCR6 Expression |
| Th17 cells |
High |
| Memory T cells |
Moderate |
| B cells |
Moderate |
| Dendritic cells |
Low-moderate |
| Regulatory T cells |
Some subsets |
In the CNS, CCR6 is primarily expressed on:
- Infiltrating Th17 cells
- Some activated astrocytes (in disease)
- Dendritic cells in meninges
- Perivascular macrophages
- Highest: Secondary lymphoid organs
- High: Intestine, skin
- Moderate: Lung, liver
- Low: Most other tissues
CCR6 activates multiple signaling cascades:
- Gαi signaling: Inhibits adenylate cyclase
- MAPK pathway: ERK1/2 activation
- PI3K/Akt: Survival and migration
- NF-κB: Pro-inflammatory gene expression
- Rho GTPases: Actin cytoskeleton remodeling
CCR6 as a therapeutic target[ccr62023]:
- Monoclonal antibodies: Anti-CCR6 in clinical trials
- Small molecule antagonists: Pre-clinical development
- Decoy receptors: CCL20 traps
CCR6 as a biomarker:
- Disease activity in MS and RA
- Treatment response
- Prognostic indicator