¶ CCL20 (C-C Motif Chemokine Ligand 20)
CCL20 (C-C Motif Chemokine Ligand 20), also known as Macrophage Inflammatory Protein-3α (MIP-3α) and Exodus-1, is a chemokine that functions as a potent chemoattractant for lymphocytes and dendritic cells. CCL20 is unique among chemokines as it signals through CCR6, its only known receptor. In the central nervous system, CCL20 is expressed in various cell types and plays important roles in neuroinflammation, immune cell recruitment to the CNS, and has been implicated in the pathogenesis of neurodegenerative diseases.
|
|
| Symbol |
CCL20 |
| NCBI Gene ID |
6384 |
| Chromosome |
2q36.3 |
| Protein Class |
Chemokine |
| Molecular Weight |
~8 kDa |
CCL20 has distinct functions in immune and nervous systems:
- Lymphocyte recruitment: Potent chemoattractant for CD4+ T cells, B cells, and regulatory T cells
- Dendritic cell trafficking: Guides dendritic cells to lymphoid organs
- Inflammatory response: Upregulated at sites of inflammation
- Neuroinflammation: Mediates immune cell recruitment to CNS in neurodegenerative diseases
- Microglial activation: CCL20 can activate microglia and induce inflammatory cytokine production
- Blood-brain barrier: May modulate BBB permeability
CCL20 signals through a single known receptor:
- CCR6 (CC Chemokine Receptor 6): The only known receptor for CCL20
- Expression: CCR6 is expressed on Th17 cells, regulatory T cells, B cells, and dendritic cells
- Signaling: Gαi protein-mediated signaling leading to calcium flux, chemotaxis, and cell activation
CCL20/CCR6 activates multiple intracellular cascades:
- Gαi signaling: Inhibits adenylate cyclase, reduces cAMP
- PLC-IP3 pathway: Calcium mobilization
- PI3K/Akt pathway: Cell survival and migration
- MAPK/ERK pathway: Cell proliferation and differentiation
- JAK/STAT pathway: Gene transcription
- Alzheimer's Disease: CCL20 elevated in AD brain and CSF; correlates with disease progression; may recruit inflammatory cells to amyloid plaques
- Parkinson's Disease: Increased CCL20 in substantia nigra of PD patients; involved in neuroinflammation
- Multiple Sclerosis: CCL20 implicated in Th17 cell recruitment to CNS lesions; potential therapeutic target
- Amyotrophic Lateral Sclerosis: Elevated in ALS patients; contributes to inflammatory environment
- Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
- Rheumatoid arthritis
- Certain cancers (colorectal, breast, lung)
- Psoriasis
CCL20 expression is inducible and cell-type specific:
| Cell Type |
Expression Level |
Notes |
| Neurons |
Low-Moderate |
Constitutive, upregulated in disease |
| Astrocytes |
High |
Strongly inducible by inflammatory stimuli |
| Microglia |
Moderate-High |
Constitutive expression |
| Endothelial cells |
High |
BBB and vascular endothelium |
| Epithelial cells |
High |
Intestinal and bronchial epithelium |
CCL20 expression is tightly regulated:
- NF-κB: Primary inducible transcription factor
- AP-1: Cooperates with NF-κB
- STAT3: Inflammatory signaling
- TNF-α: Strong inducer of CCL20 expression
- IL-1β: Synergistic with TNF-α
The CCL20/CCR6 axis is being explored for therapy:
- CCR6 antagonists: Anti-CCR6 antibodies in development for autoimmune diseases
- Neutralizing antibodies: Anti-CCL20 antibodies researched for inflammatory conditions
- Small molecule inhibitors: CCR6 antagonists in pre-clinical and clinical trials