CCR6

CCR6

<div class="infobox infobox-gene">
<div class="infobox-header">CCR6</div>
<div class="infobox-row"><span>Full Name:</span> C-C Chemokine Receptor Type 6</div>
<div class="infobox-row"><span>Gene Symbol:</span> CCR6</div>
<div class="infobox-row"><span>Aliases:</span> CD196, BN-1, DWR</div>
<div class="infobox-row"><span>Chromosomal Location:</span> 6q27</div>
<div class="infobox-row"><span>NCBI Gene ID:</span> 1235</div>
<div class="infobox-row"><span>OMIM:</span> 603526</div>
<div class="infobox-row"><span>Ensembl ID:</span> ENSG00000112486</div>
<div class="infobox-row"><span>UniProt ID:</span> P51671</div>
<div class="infobox-row"><span>Protein Length:</span> 374 amino acids</div>
</div>

Overview

CCR6

<div class="infobox infobox-gene">
<div class="infobox-header">CCR6</div>
<div class="infobox-row"><span>Full Name:</span> C-C Chemokine Receptor Type 6</div>
<div class="infobox-row"><span>Gene Symbol:</span> CCR6</div>
<div class="infobox-row"><span>Aliases:</span> CD196, BN-1, DWR</div>
<div class="infobox-row"><span>Chromosomal Location:</span> 6q27</div>
<div class="infobox-row"><span>NCBI Gene ID:</span> 1235</div>
<div class="infobox-row"><span>OMIM:</span> 603526</div>
<div class="infobox-row"><span>Ensembl ID:</span> ENSG00000112486</div>
<div class="infobox-row"><span>UniProt ID:</span> P51671</div>
<div class="infobox-row"><span>Protein Length:</span> 374 amino acids</div>
</div>

Overview

CCR6 encodes a G protein-coupled receptor for CCL20 (MIP-3alpha/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](/entities/th17-cells) trafficking, B cell migration, and dendritic cell positioning. Variants in CCR6 have been implicated in [Multiple Sclerosis](/diseases/multiple-sclerosis), [Parkinson's Disease](/diseases/parkinsons-disease), [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis), and various autoimmune conditions including inflammatory bowel disease, rheumatoid arthritis, and psoriasis["ccr62019"][@ccr62018].

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.

Molecular Biology

Gene Structure

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.

Protein Structure

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](/entities/astrocytes) in the CNS
• Epithelial cells
• Dendritic cells
• Fibroblasts
• Activated T cells

Function

Th17 Cell Trafficking

CCR6 is a defining marker for [Th17 cells](/entities/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

B Cell Trafficking

CCR6 regulates B lymphocyte migration[ccr62019b]:

• Migration to secondary lymphoid organs
• Positioning in germinal centers
• Plasma cell differentiation

Dendritic Cell Function

Dendritic cell CCR6[ccr62018]:

• Guides positioning in tissues
• Lymph node migration
• T cell priming

Mucosal Immunity

In mucosal tissues:

• Recruitment of immune cells to gut-associated lymphoid tissue
• Maintenance of intestinal immune homeostasis
• Defense against pathogens

T Cell Development

CCR6 in T cell biology[ccr62018b]:

• Memory T cell maintenance
• Regulatory T cell trafficking
• γδ T cell function

Disease Associations

Multiple Sclerosis

CCR6 is a major player in MS pathogenesis[ccr62017][@ccr62020]:

| 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 |

Parkinson's Disease

CCR6 in PD[ccr62021]:

• Increased CCR6+ T cells in PD patients
• CCL20 elevated in substantia nigra
• Contribution to dopaminergic neuron loss
• Potential biomarker

Amyotrophic Lateral Sclerosis

CCR6 in ALS[ccr62024]:

• Elevated CCR6+ T cells in ALS patients
• CCR6+ T cells in spinal cord
• Contributes to motor neuron damage

Inflammatory Bowel Disease

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

Rheumatoid Arthritis

CCR6 in RA[ccr62022]:

• Th17 cells via CCR6 infiltrate joints
• CCL20 expressed in rheumatoid synovium
• Therapeutic targeting in development

Psoriasis

CCR6 in psoriasis[ccr62015]:

• CCR6+ Th17 cells in skin lesions
• CCL20 upregulated in psoriatic skin
• Clinical trials of CCR6 antagonists

Expression

Immune Cell Expression

| Cell Type | CCR6 Expression |
|-----------|-----------------|
| Th17 cells | High |
| Memory T cells | Moderate |
| B cells | Moderate |
| Dendritic cells | Low-moderate |
| Regulatory T cells | Some subsets |

Brain Expression

In the CNS, CCR6 is primarily expressed on:

• Infiltrating Th17 cells
• Some activated [astrocytes](/entities/astrocytes) (in disease)
• Dendritic cells in meninges
• Perivascular macrophages

Tissue Distribution

• Highest: Secondary lymphoid organs
• High: Intestine, skin
• Moderate: Lung, liver
• Low: Most other tissues

Signaling Pathways

CCR6 activates multiple signaling cascades:

Therapeutic Implications

Drug Development

CCR6 as a therapeutic target[ccr62023]:

• Monoclonal antibodies: Anti-CCR6 in clinical trials
• Small molecule antagonists: Pre-clinical development
• Decoy receptors: CCL20 traps

Biomarkers

CCR6 as a biomarker:

• Disease activity in MS and RA
• Treatment response
• Prognostic indicator

See Also

• [CCL20](/genes/ccl20)
• [Th17 Cells](/entities/th17-cells)
• [Multiple Sclerosis](/diseases/multiple-sclerosis)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Neuroinflammation](/mechanisms/neuroinflammation-pathway)
• [Autoimmunity](/mechanisms/autoimmunity-pathway)

External Links

• [NCBI Gene: CCR6](https://www.ncbi.nlm.nih.gov/gene/1235)
• [UniProt: CCR6](https://www.uniprot.org/uniprot/P51671)
• [OMIM: CCR6](https://www.omim.org/entry/603526)
• [Ensembl: CCR6](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000112486)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving CCR6 discovered through SciDEX knowledge graph analysis: