CCL20

Chemokine (C-C motif) ligand 20 (CCL20) or liver activation regulated chemokine (LARC) or Macrophage Inflammatory Protein-3 (MIP3A) is a small cytokine belonging to the CC chemokine family. It is strongly chemotactic for lymphocytes and weakly attracts neutrophils.^[5] CCL20 is implicated in the formation and function of mucosal lymphoid tissues via chemoattraction of lymphocytes and dendritic cells towards the epithelial cells surrounding these tissues. CCL20 elicits its effects on its target cells by binding and activating the chemokine receptor CCR6.^[6]

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CCL20
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2JYO, 1M8A, 2HCI
Identifiers
Aliases	CCL20, CKb4, Exodus, LARC, MIP-3-alpha, MIP-3a, MIP3A, SCYA20, ST38, chemokine (C-C motif) ligand 20, C-C motif chemokine ligand 20
External IDs	OMIM: 601960; MGI: 1329031; HomoloGene: 3375; GeneCards: CCL20; OMA:CCL20 - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q36.3 Start 227,805,739 bp[1] End 227,817,564 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1 C5|1 42.69 cM Start 83,094,487 bp[2] End 83,096,888 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in epithelium of nasopharynx cartilage tissue gallbladder secondary oocyte appendix rectum beta cell mucosa of sigmoid colon sperm testicle Top expressed in embryo duodenum embryo thymus jejunum colon trachea ileum lip left colon More reference expression data BioGPS More reference expression data
Gene ontology Molecular function cytokine activity protein binding CCR6 chemokine receptor binding chemokine activity CCR chemokine receptor binding Cellular component extracellular region intracellular anatomical structure extracellular space Biological process monocyte chemotaxis positive regulation of T cell migration neutrophil chemotaxis positive regulation of ERK1 and ERK2 cascade positive regulation of GTPase activity positive regulation of nitric-oxide synthase biosynthetic process defense response to bacterium cell-cell signaling lymphocyte chemotaxis wound healing cellular response to lipoteichoic acid cellular response to tumor necrosis factor cellular response to organic substance chemokine-mediated signaling pathway cellular response to interleukin-1 cellular response to interferon-gamma signal transduction immune response cellular response to lipopolysaccharide chemotaxis calcium-mediated signaling using intracellular calcium source cell chemotaxis T cell migration thymocyte migration inflammatory response antimicrobial humoral immune response mediated by antimicrobial peptide regulation of signaling receptor activity G protein-coupled receptor signaling pathway cytokine-mediated signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6364 20297 Ensembl ENSG00000115009 ENSMUSG00000026166 UniProt P78556 O89093 RefSeq (mRNA) NM_004591 NM_001130046 NM_001159738 NM_016960 RefSeq (protein) NP_001123518 NP_004582 NP_001153210 NP_058656 Location (UCSC) Chr 2: 227.81 – 227.82 Mb Chr 1: 83.09 – 83.1 Mb PubMed search [3] [4]
Wikidata
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Gene expression of CCL20 can be induced by microbial factors such as lipopolysaccharide (LPS), and inflammatory cytokines such as tumor necrosis factor and interferon-γ, and down-regulated by IL-10.^[7] CCL20 is expressed in several tissues with highest expression observed in peripheral blood lymphocytes, lymph nodes, liver, appendix, and fetal lung and lower levels in thymus, testis, prostate and gut.^[5][8] The gene for CCL20 (scya20) is located on chromosome 2 in humans.^[9]

Recent research ^[10] in an animal model of multiple sclerosis known as experimental autoimmune encephalitis (EAE) demonstrated that regional neural activation can create "gates" for pathogenic CD4+ T cells to enter the CNS by increasing CCL20 expression, especially at L5. Sensory nerve stimulation, elicited by using muscles in the leg or electrical stimulation as in Arima et al., 2012, activates sympathetic neurons whose axons run through the dorsal root ganglia containing cell bodies of the stimulated afferent sensory nerve. Sympathetic neuronal activity activates IL-6 amplifier resulting in increased regional CCL20 expression and subsequent pathogenic CD4+ T cell accumulation at the same spinal cord level. CCL20 expression was observed to be dependent on IL-6 amplifier activation, which is dependent on NF-κB and STAT3 activation. This research provides evidence for a critical role for CCL20 in autoimmune pathogenesis of the central nervous system.