CCL20 (C-C Motif Chemokine Ligand 20), also known as Macrophage Inflammatory Protein-3alpha (MIP-3alpha) 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["@schutyser2003"][@williams2008].
Gene Overview
Function
CCL20 has distinct functions in immune and nervous systems:
Immune System
Lymphocyte recruitment: Potent chemoattractant for CD4+ T cells, B cells, and regulatory T cells[@brenner2004]
Dendritic cell trafficking: Guides dendritic cells to lymphoid organs
Inflammatory response: Upregulated at sites of inflammation
Nervous System
Neuroinflammation: Mediates immune cell recruitment to CNS in neurodegenerative diseases[@stuart2015]
Microglial activation: CCL20 can activate [microglia](/cell-types/microglia-neuroinflammation) and induce inflammatory cytokine production
[Blood-brain barrier](/entities/blood-brain-barrier): May modulate BBB permeability
Receptor
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
MAPK/ERK pathway: Cell proliferation and differentiation
JAK/STAT pathway: Gene transcription
Disease Associations
Neurodegenerative Diseases
Alzheimer's Disease: CCL20 elevated in AD brain and CSF; correlates with disease progression; may recruit inflammatory cells to amyloid plaques[@brennan2011]
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[@ccl2010]
Amyotrophic Lateral Sclerosis: Elevated in ALS patients; contributes to inflammatory environment