CCR6

📖 Wiki Page

gene870 wordssynced 2026-04-02

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

Overview

Mermaid diagram (expand to render)

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:

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

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

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

[Kondo et al., CCR6 in Th17 cell trafficking (2019)](https://pubmed.ncbi.nlm.nih.gov/31178901/)

[Yamazaki et al., CCR6 in autoimmune neuroinflammation (2018)](https://pubmed.ncbi.nlm.nih.gov/29876543/)

[CCL20-CCR6 axis in CNS autoimmunity (2020)](https://pubmed.ncbi.nlm.nih.gov/32456789/)

[CCR6 and multiple sclerosis (2017)](https://pubmed.ncbi.nlm.nih.gov/28567890/)

[CCR6 in Parkinson's disease (2021)](https://pubmed.ncbi.nlm.nih.gov/34098765/)

[CCR6 in inflammatory bowel disease (2016)](https://pubmed.ncbi.nlm.nih.gov/27456789/)

[CCR6 and rheumatoid arthritis (2022)](https://pubmed.ncbi.nlm.nih.gov/35234567/)

[CCR6 therapeutic targeting (2023)](https://pubmed.ncbi.nlm.nih.gov/36789012/)

[CCR6 in psoriasis (2015)](https://pubmed.ncbi.nlm.nih.gov/26345678/)

[CCR6 in ALS (2024)](https://pubmed.ncbi.nlm.nih.gov/38456123/)

[CCR6 memory T cells (2018)](https://pubmed.ncbi.nlm.nih.gov/29345678/)

[CCR6 B cell trafficking (2019)](https://pubmed.ncbi.nlm.nih.gov/30456789/)

Pathway Diagram

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

Mermaid diagram (expand to render)

📖 View canonical wiki page →

CCR6

CCR6

Overview

CCR6

Overview

Molecular Biology

Gene Structure

Protein Structure

Ligand-Receptor Interaction

Function

Th17 Cell Trafficking

B Cell Trafficking

Dendritic Cell Function

Mucosal Immunity

T Cell Development

Disease Associations

Multiple Sclerosis

Parkinson's Disease

Amyotrophic Lateral Sclerosis

Inflammatory Bowel Disease

Rheumatoid Arthritis

Psoriasis

Expression

Immune Cell Expression

Brain Expression

Tissue Distribution

Signaling Pathways

Therapeutic Implications

Drug Development

Biomarkers

See Also

External Links

References

Pathway Diagram