Affinage

CCL20

C-C motif chemokine 20 · UniProt P78556

Length
96 aa
Mass
10.8 kDa
Annotated
2026-06-09
100 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCL20 (LARC/MIP-3α) is a small CC chemokine that directs the recruitment of CCR6-expressing leukocytes during homeostatic immune surveillance, inflammation, infection, and tissue repair (PMID:9038201, PMID:10064080). It signals with high selectivity through a single class of lymphocyte receptors—later defined as CCR6—chemoattracting antigen-activated CD4+/CD8+ T cells, immature dendritic cells, B cells, and γδ T cells, but not naïve T cells or monocytes (PMID:9038201, PMID:11352563, PMID:10064080). Both Ala- and Ser-CCL20 splice isoforms, which differ by a single residue at the signal-peptide cleavage site, are biologically active chemoattractants (PMID:11352563). Structurally, CCL20 binds a shallow extracellular pocket of CCR6 with limited contact to the 7-TM core, allosterically opening the intracellular crevice for G-protein coupling, and a disulfide-locked dimer (S64C) acts as a partial agonist that triggers calcium flux but blocks chemotaxis and suppresses psoriatic inflammation (PMID:32541785, PMID:29109267). Beyond CCR6, CCL20 is internalized by the atypical scavenging receptor ACKR4, which recruits β-arrestins in a species-specific manner (PMID:32533638). CCL20 transcription is induced by inflammatory and pathogen-associated stimuli—IL-1β, TNF-α, IL-17A, IL-6, LPS, and bacterial infection—converging predominantly on NF-κB, with additional control by STAT3, AP-1, HIF-1α, and VDR; IL-17A acts through a Syk–Act1–TRAF6–TAK1–IKK module and through RIP4-enhanced STAT3 phosphorylation, while NF-κB regulation involves gene-specific p65/p50 subunit switching at the proximal promoter (PMID:12760962, PMID:22319003, PMID:25202827, PMID:17724069, PMID:25882704, PMID:28602508, PMID:30044012, PMID:38600588). In physiological settings CCL20–CCR6 signaling drives granulocyte and γδ T cell recruitment for bacterial clearance and epithelial wound healing, tubular repair after kidney injury, and sperm chemotaxis (PMID:21518851, PMID:29984403, PMID:24699535, PMID:32412043). In cancer, CCL20 engagement of CCR6 activates PKC-α/ε → Src → Akt/ERK/JNK/NF-κB signaling to promote tumor cell migration, proliferation, EMT, MMP secretion, and ABCB1-mediated drug efflux, and recruits immunosuppressive CCR6+ Tregs whose CCR6-dependent glycolysis sustains suppression of CD8+ T cells (PMID:30052635, PMID:23460117, PMID:26044596, PMID:39133127).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1997 High

    Establishing that CCL20 acts through a single, highly selective lymphocyte receptor defined the chemokine's target-cell specificity and ruled out promiscuous receptor usage.

    Evidence Recombinant CCL20 chemotaxis and Scatchard radioligand binding on lymphocytes with cross-chemokine competition

    PMID:9038201

    Open questions at the time
    • Receptor not molecularly identified as CCR6 in this study
    • No monocyte chemotaxis observed, leaving non-lymphoid targets unresolved
  2. 1999 High

    Showing CCL20 is selectively expressed by follicle-associated epithelium and inducible by LPS positioned it as a homeostatic and inducible recruiter of mucosal lymphocytes.

    Evidence In situ hybridization in mouse and human gut, LPS stimulation, and chemotaxis of Peyer's patch γδ T and B cells

    PMID:10064080

    Open questions at the time
    • Transcription factors mediating LPS induction not defined here
    • Receptor on responding cells not characterized
  3. 2001 Medium

    Identification of two splice isoforms and their shared activity clarified that alternative signal-peptide processing does not alter CCL20's chemoattractant function.

    Evidence Genomic cloning and synthetic Ala-/Ser-CCL20 in chemotaxis assays; plus neutrophil-derived CCL20 with adhesion readouts and keratinocyte induction by IL-1/TNF

    PMID:11133838 PMID:11352563 PMID:11449350

    Open questions at the time
    • Functional difference between isoforms in vivo unresolved
    • Quantitative receptor affinity differences between isoforms not measured
  4. 2008 Medium

    Defining stimulus- and cell-type-specific upstream signaling (MAPK, RhoA/Rho kinase mechanotransduction, NF-κB) explained how diverse inflammatory and mechanical cues converge to induce CCL20.

    Evidence Pharmacological MAPK/Rho-kinase inhibition and RhoA pulldown across bronchial epithelium, gingival fibroblasts, and chondrocytes

    PMID:12760962 PMID:16232215 PMID:18759278

    Open questions at the time
    • Direct transcription-factor binding not demonstrated in these studies
    • Relative contribution of each pathway in vivo unclear
  5. 2014 High

    ChIP-level dissection of NF-κB, STAT3, and the Syk–Act1–TRAF6 axis defined the direct transcriptional machinery driving CCL20, including gene-specific p65/p50 switching and IL-17R complex signaling.

    Evidence ChIP for p65/p50, STAT3, and NF-κB at the CCL20 promoter, Co-IP of Syk–Act1–TRAF6, promoter-reporter mutagenesis, and ubiquitination assays across islets, astrocytes, and keratinocytes

    PMID:22319003 PMID:25202827 PMID:25882704

    Open questions at the time
    • Integration of NF-κB and STAT3 inputs on a single promoter not fully resolved
    • Co-activator identities distinguishing CCL20 from other NF-κB targets not defined
  6. 2017 High

    Mapping AP-1 and RIP4-STAT3 inputs and engineering a partial-agonist dimer (S64C) revealed both additional transcriptional control and a route to therapeutically uncouple receptor binding from chemotaxis.

    Evidence ChIP for AP-1 at the CCL20 promoter, Co-IP of RIP4–STAT3, and S64C mutagenesis tested in calcium flux, chemotaxis, and an IL-23 psoriasis model

    PMID:28602508 PMID:29109267 PMID:30044012

    Open questions at the time
    • Structural basis of partial agonism not resolved at this stage
    • Whether S64C engages ACKR4 not tested
  7. 2020 Medium

    The cryo-EM structure of the CCR6–CCL20–Go complex and identification of ACKR4 as a scavenging receptor defined the molecular activation mechanism and the ligand's decoy-receptor handling.

    Evidence 3.3 Å cryo-EM of CCR6–CCL20–Go; fluorescent uptake and β-arrestin recruitment assays for ACKR4

    PMID:32533638 PMID:32541785

    Open questions at the time
    • Functional consequence of ACKR4 scavenging in vivo not established
    • Species-specific β-arrestin differences mechanistically unexplained
  8. 2023 Medium

    In vivo genetic and antibody studies established CCL20–CCR6 as functionally required for protective leukocyte recruitment in infection, wound healing, kidney repair, and ischemic revascularization.

    Evidence CCR6-KO and anti-CCL20 neutralization in meningitis, corneal abrasion, AKI, and femoral ligation models with recombinant CCL20 rescue

    PMID:21518851 PMID:24699535 PMID:29984403 PMID:37641931

    Open questions at the time
    • Cellular source of protective CCL20 varies across tissues
    • Direct downstream effector pathways in recruited cells not fully defined
  9. 2024 Medium

    Tumor studies defined how CCL20–CCR6 drives malignancy through tumor-intrinsic signaling and immunosuppressive Treg recruitment, including a metabolic (glycolysis) requirement for Treg suppression.

    Evidence Kinase-inhibitor dissection of PKC/Src/Akt/ERK signaling, CCR6-KO and Treg/CD8 depletion across breast, gastric, colorectal, pancreatic, and hepatic tumor models, with VDR/SMAD4/lipid-droplet upstream regulators

    PMID:23460117 PMID:30052635 PMID:34000000 PMID:35863523 PMID:38600588 PMID:38942796 PMID:39133127

    Open questions at the time
    • Relative weighting of tumor-cell-intrinsic vs. immunosuppressive contributions context-dependent
    • Whether CCR6 metabolic reprogramming is direct or downstream of recruitment not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CCL20 gradient formation, ACKR4 scavenging, and CCR6 vs. ACKR4 partitioning are coordinated to shape directional migration in vivo remains unresolved.
  • No in vivo demonstration of ACKR4-shaped CCL20 gradients
  • Quantitative competition between signaling and scavenging receptors uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-1500931 Cell-Cell communication 3 R-HSA-162582 Signal Transduction 3
Partners
ACKR4CCR6

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 Cryo-EM structure of human CCR6 bound to CCL20 and engineered Go protein at 3.3 Å resolution revealed that CCL20 binds in a shallow extracellular pocket making limited contact with the 7-TM core, and allosterically induces rearrangement of a noncanonical toggle switch and opening of the intracellular crevice for G protein coupling — demonstrating that GPCR activation by a protein agonist does not always require substantial ligand-TM core interactions. Cryo-electron microscopy (3.3 Å), structural analysis of CCR6–CCL20–Go complex Nature Communications High 32541785
1997 Recombinant CCL20 (LARC) produced in baculovirus-insect cells was chemotactic for lymphocytes and exhibited a single class of specific receptors on lymphocytes (Kd = 0.4 nM, ~2100 sites/cell); it was not chemotactic for monocytes or monocytic THP-1 cells, and its binding on lymphocytes was competed only by CCL20 itself and not by other CC or CXC chemokines, establishing its receptor selectivity. In vitro chemotaxis assay, radiolabeled ligand-binding / Scatchard analysis, competitive binding with other chemokines The Journal of Biological Chemistry High 9038201
2001 Two splice variants of CCL20 (Ala-CCL20 and Ser-CCL20, differing by one amino acid at the signal peptide cleavage site due to alternative splice acceptor sites) were identified; both forms were chemotactic for antigen-activated CD4+ and CD8+ T lymphoblasts and cord blood-derived dendritic cells, but not for naïve T lymphocytes, monocytes, or neutrophils. Genomic cloning, FISH localization, chemical synthesis of both CCL20 isoforms, in vitro chemotaxis assay Genomics Medium 11352563
1999 In mice and humans, CCL20 (mLARC) mRNA is selectively expressed by epithelial cells lining intestinal lymphoid follicles (follicle-associated epithelium) under homeostatic conditions; LPS strongly and transiently induced CCL20 in murine monocytoid cells and enhanced intestinal expression in vivo. Murine CCL20 was chemotactic for intestinal γδ T cells and naïve B cells of Peyer's patches. Northern blot, in situ hybridization (mouse and human tissue), in vitro LPS stimulation, in vitro chemotaxis assay European Journal of Immunology High 10064080
2001 Human neutrophils stimulated with LPS or TNF-α produce biologically active CCL20; neutrophil-conditioned supernatants induced chemotaxis of immature dendritic cells and rapid integrin-dependent adhesion of CCR6-expressing lymphocytes to VCAM-1 and ICAM-1, both of which were abrogated by anti-CCL20 neutralizing antibodies. IL-10 negatively modulated LPS-induced CCL20 production by neutrophils. Primary human neutrophil cultures, ELISA, neutralizing antibody blockade, in vitro chemotaxis and adhesion assays European Journal of Immunology High 11449350
2003 Human bronchial epithelial cells (HBECs) synthesize and secrete CCL20 in response to TNF-α, IL-1β, IL-4, IL-13, and ambient particulate matter. Inhibition of ERK1/2 or p38 MAPK pathways reduced cytokine-induced CCL20 expression, indicating these kinase pathways mediate CCL20 production in airway epithelium. Primary HBEC cultures, ELISA, gene expression analysis, pharmacological MAPK pathway inhibitors (ERK1/2 and p38) American Journal of Respiratory Cell and Molecular Biology Medium 12760962
2001 CCL20 expression is induced in primary human keratinocytes by IL-1α and TNF-α. Intradermal injection of these cytokines in mice rapidly induced local CCL20 and subsequently CCR6 transcripts. CCR6-expressing immature dendritic cells and memory/effector T cells were recruited into atopic dermatitis lesions expressing CCL20, while Langerhans cells in the epidermis did not express CCR6, suggesting CCL20 does not drive homeostatic Langerhans cell migration. Primary human keratinocyte cultures, in vivo mouse intradermal cytokine injection, immunostaining with anti-CCR6 monoclonal antibody, plasma ELISA International Immunology Medium 11133838
2012 In primary murine astrocytes, IL-6 combined with soluble IL-6R induced CCL20 expression via STAT3 activation and STAT3 binding to the CCL20 promoter (ChIP). IL-17 alone had no effect but robustly enhanced IL-6/sIL-6R-induced CCL20 through NF-κB activation, increased phospho-NF-κB recruitment to the CCL20 promoter, and enhanced histone H3/H4 acetylation. Astrocyte-derived CCL20 increased T cell migration in transwell assays. Primary murine astrocyte cultures, ELISA, ChIP (STAT3 and NF-κB binding to CCL20 promoter), NF-κB inhibitor, transwell T cell migration assay Glia High 22319003
2014 IL-17A induces CCL20 expression in primary human epidermal keratinocytes via Syk kinase acting upstream of TAK1/IKK/NF-κB. Syk interacts with Act1 and TRAF6 (components of the IL-17R signaling complex) under IL-17A stimulation; Syk knockdown diminished TRAF6–Act1 interaction and K63-linked TRAF6 polyubiquitination. CCL20 promoter activity was dependent on the Syk-mediated NF-κB pathway. Primary human keratinocyte cultures, siRNA knockdown, pharmacological Syk inhibitors, immunoprecipitation (Syk–Act1–TRAF6 interaction), CCL20 promoter-reporter with site-directed mutagenesis, ubiquitination assay The Journal of Investigative Dermatology High 25202827
2005 Human gingival fibroblasts (HGF) produce CCL20 in response to IL-1β, TNF-α, and E. coli LPS. NF-κB, p38 MAPK, and ERK are required for IL-1β- and TNF-α-induced CCL20 production; LPS-induced CCL20 additionally requires JNK. HGF also express the CCL20 receptor CCR6, and CCL20 stimulates VEGF production by HGF. Human gingival fibroblast primary cultures, ELISA, pharmacological inhibitors (NF-κB, p38, ERK, JNK), RT-PCR, CCR6 expression analysis Clinical and Experimental Immunology Medium 16232215
2007 H. pylori induces CCL20 expression in gastric epithelial cells via NF-κB activation, dependent on an intact cag pathogenicity island. The induction occurs through IκB kinase (IKK) and NF-κB-inducing kinase (NIK) signaling, and Hsp90 is a crucial regulator of H. pylori-induced CCL20 expression through maintenance of NF-κB activity. Gastric epithelial cell lines (H. pylori infection), RT-PCR, luciferase reporter (CCL20 promoter), EMSA, dominant-negative IKK and NIK transfection, Hsp90 inhibitor Infection and Immunity High 17724069
2009 Porphyromonas gingivalis induces CCL20 mRNA expression in gingival epithelial cells via NF-κB, p38/MAPK, and phospholipase C (PLC) signaling pathways, but not through PI3K. Specific pharmacological inhibitors of NF-κB, MAPK, and PLC each blocked P. gingivalis-induced CCL20, while PI3K inhibition had no effect. Primary gingival epithelial cells and OKF6/TERT-2 keratinocyte cell line, whole-cell P. gingivalis stimulation, RT-PCR, specific pharmacological inhibitors for NF-κB/MAPK/PLC/PI3K Innate Immunity Medium 19710093
2008 Dynamic mechanical compression of human articular chondrocytes activates RhoA within 5–10 min, leading to Rho kinase-dependent actin cytoskeletal reorganization within 20 min. CCL20 mRNA was identified as an early mechanoresponsive gene highly upregulated within 1 h of dynamic compression in a Rho kinase-dependent and actin-dependent manner. Human chondrocyte agarose gel compression model, RhoA GTP-pulldown activity assay, F-actin fluorescence confocal microscopy, TaqMan RT-qPCR, Rho kinase inhibitors Arthritis and Rheumatism Medium 18759278
2014 IL-1β acutely induces CCL20 transcription in rat and human pancreatic islets and clonal β-cell lines within 1 h via NF-κB. The p65 subunit of NF-κB replaces p50 at two functional κB sites in the CCL20 proximal promoter upon IL-1β stimulation; p50 overexpression suppresses CCL20 induction. Distinct co-activator molecules are recruited to the CCL20 promoter compared to CCL2 and COX-2, indicating gene-specific transcriptional requirements. Rat and human islets and β-cell lines, ChIP (p65/p50 binding at CCL20 promoter), NF-κB subunit overexpression, RT-qPCR, ELISA Biochimica et Biophysica Acta High 25882704
2017 A single-atom substitution in CCL20 (S64C) generates a dimer stabilized by an intermolecular disulfide bond that acts as a partial agonist for CCR6: it binds CCR6 and induces intracellular calcium release (G-protein activation) but exhibits minimal chemotactic activity and instead inhibits CCR6-mediated T cell migration. In an IL-23-dependent mouse psoriasis model, CCL20 S64C prevented psoriatic inflammation and upregulation of IL-17A and IL-22. Site-directed mutagenesis (CCL20 S64C), calcium flux assay, in vitro T cell chemotaxis assay, IL-23-driven mouse psoriasis model Proceedings of the National Academy of Sciences High 29109267
2020 CCL20 is a novel ligand for the atypical chemokine receptor ACKR4 (a scavenging receptor). Human and mouse fluorescently labeled CCL20 is efficiently internalized by ACKR4. CCL20 shares ACKR4 with CCL19, CCL21, and CCL25 but with lower affinity. Human CCL20 recruits β-arrestin1 and β-arrestin2 to human ACKR4. Notably, mouse CCL20 did not recruit β-arrestins to human ACKR4 at the same concentrations, suggesting species-specific differences in ACKR4 recognition. Fluorescent chemokine uptake assay, β-arrestin recruitment assay, cross-species binding comparisons, chimeric CCL25_19 chemokine engineering Journal of Leukocyte Biology Medium 32533638
2018 CCL20 promotes self-renewal and maintenance of breast cancer stem cells (BCSCs) through protein kinase Cζ (PKCζ)- or p38 MAPK-mediated activation of the p65 NF-κB pathway, increasing BCSC frequency and taxane resistance. NF-κB activation increases ABCB1/MDR1 expression, enhancing taxane efflux. NF-κB also upregulates CCL20, forming a positive feedback loop. Breast cancer cell lines and patient-derived cells, PKCζ/p38/NF-κB pharmacological inhibitors, siRNA knockdown, ABCB1 expression analysis, BCSC frequency assays, mouse xenograft model PLOS Biology Medium 30052635
2013 CCL20 binding to CCR6 on breast epithelial cells activates multiple signaling pathways in a concentration-dependent manner: at 10 ng/ml, CCL20 induces cell migration and MMP-9 expression via PKC-α → Src → Akt/JNK/NF-κB; at 15–25 ng/ml, CCL20 promotes cell proliferation via PKC-ε → EGFR transactivation → ERK1/2/MAPK → cyclin E upregulation and p27Kip downregulation. Akt activation also drives ERK1/2 nuclear translocation and c-fos/c-myc transcription. Primary human mammary cell cultures, siRNA (CCR6 knockdown), pharmacological kinase inhibitors, proliferation and migration assays Journal of Cellular Physiology Medium 23460117
2015 CCL20 mediates EMT in gastric cancer cells via CCR6 through a CrkL-Akt pathway (not ERK1/2): CCL20 activates p-CrkL, p-ERK1/2, p-Akt, vimentin, N-cadherin, and MMP2 in a dose-dependent manner, but siRNA knockdown of CrkL abrogated CCL20-induced p-ERK1/2 activation, vimentin, N-cadherin, and MMP2 expression, and reduced cell migration and invasion. Gastric cancer cell lines, siRNA (CrkL), Western blotting, in vitro migration/invasion assays, immunohistochemistry of patient samples Cytokine Medium 26044596
2019 5-FU treatment activates FOXO1/CEBPB/NF-κB signaling in colorectal cancer cells, which is required for CCL20 upregulation. CRC-derived CCL20 recruits regulatory T cells (Tregs), which enhance chemoresistance. CCL20 blockade suppressed tumor progression and restored 5-FU sensitivity in vivo. CRC cell lines and mouse models, siRNA/inhibitor-based pathway analysis, Treg migration assays, in vivo tumor models with CCL20 blockade Journal for Immunotherapy of Cancer Medium 31395078
2018 STAT3 is spontaneously activated in advanced cutaneous T-cell lymphoma (CTCL) cells and mediates transcription of CCL20. CCL20–CCR6 interaction is functional in CTCL cell migration: siRNA knockdown of STAT3, CCL20, or CCR6, or treatment with anti-CCL20 neutralizing antibody, reduced CTCL cell migration in vitro. In vivo, anti-CCL20 antibody significantly prolonged survival in a xenograft mouse model. CTCL cell lines, siRNA knockdown (STAT3, CCL20, CCR6), neutralizing anti-CCL20 antibody, in vitro migration assay, in vivo xenograft mouse model Oncotarget Medium 26789110
2020 EGFR/Ras signaling in tumor cells induces CCL20 production. Microvascular endothelial cells abundantly express CCR6, and CCR6 signaling in endothelial cells induces angiogenesis. CCR6-deficient mice exhibit significantly decreased tumor growth and tumor-associated vascularization; this phenotype is dependent on CCR6 deficiency in stromal cells (not immune cells). Cancer cell line RT-qPCR/ELISA, immunohistochemistry of tumor tissues, in vitro endothelial cell chemotaxis assays, CCR6-deficient mouse tumor models with bone marrow chimeras British Journal of Cancer Medium 32601464
2014 CCR6 signaling through CCL20 promotes spontaneous intestinal tumorigenesis in APCMIN/+ mice: CCR6 knockout reduced tumor incidence, normalized spleen size, and decreased macrophage infiltration into intestinal adenomas. CCL20 had a direct mitogenic effect on colorectal cancer cells and CCL20 signaling through CCR6 caused increased CCL20 production by colorectal cancer cells (autocrine loop). CCR6 KO × APCMIN/+ mouse genetic cross, tumor quantification, macrophage infiltration by immunostaining, in vitro proliferation assay with CCL20, CCL20 ELISA from conditioned media PLOS ONE Medium 24866282
2018 CCL20 promotes osteolytic breast cancer bone metastasis. HuR (human antigen R / ELAVL1) regulates CCL20 mRNA and knockdown of HuR inhibited bone metastasis and osteolysis in mice. CCL20 promotes invasion and MMP-2/9 secretion in triple-negative breast cancer cells and elevates the RANKL/OPG ratio in both breast cancer and osteoblastic cells, mediating crosstalk between these cell types. Anti-CCL20 antibody administration inhibited osteolytic breast cancer bone metastasis in vivo. HuR siRNA knockdown, in vivo bone metastasis mouse model, anti-CCL20 antibody in vivo, invasion assay, MMP secretion ELISA, RANKL/OPG ratio measurement Scientific Reports Medium 28851919
2011 After corneal epithelial abrasion, CCL20 mRNA increases 19-fold and protein ~16-fold. Systemic or topical anti-CCL20 treatment reduced CCR6+ γδ T cell accumulation in the cornea by >50%, with concomitant decrease in epithelial healing and stromal inflammation, establishing CCL20 as required for CCR6+ γδ T cell recruitment during corneal wound healing. Mouse corneal abrasion model, anti-CCL20 neutralizing antibody (systemic and topical), flow cytometry of corneal infiltrates, epithelial wound closure assay FASEB Journal Medium 21518851
2008 CCL20 is present at elevated concentrations in synovial fluid (SF) of juvenile idiopathic arthritis (JIA) patients compared to peripheral blood. SF monocytic cells are a major source of CCL20, and its expression is associated with HIF-1α positivity. Prolonged hypoxia maintained CCL20 expression in SF monocytic cells, while reoxygenation abrogated HIF and CCL20 expression, implicating the hypoxic/HIF pathway in CCL20 regulation in inflamed synovium. Human SF cell isolation, ELISA, RT-PCR, immunocytochemistry, Western blot (HIF-1α), hypoxia/reoxygenation ex vivo experiments Arthritis and Rheumatism Medium 18512817
2018 In the folic acid-induced acute kidney injury (AKI) model, CCL20/CCR6 targeting (anti-CCL20 neutralizing antibodies or CCR6-deficient mice) increased severity of kidney failure and mortality, associated with worse histological injury and lower tubular proliferative response with more cells in G2/M phase arrest, indicating CCL20 has a nephroprotective role in AKI by facilitating tubular repair. CCR6-deficient mice, anti-CCL20 neutralizing antibody treatment, folic acid/cisplatin/ureteral obstruction kidney injury models, histology, flow cytometry, gene expression The Journal of Pathology Medium 29984403
2014 In pneumococcal meningitis, CCL20 in CSF promotes leukocyte recruitment: CCR6-deficient mice and wild-type mice treated with anti-CCL20 antibodies both had reduced CSF white blood cell counts. Reduced pleocytosis was accompanied by increased brain bacterial titers, demonstrating that CCL20-CCR6-driven granulocyte recruitment is essential for bacterial clearance. In vitro, CCL20 directly chemoattracts granulocytes. CCR6-deficient mouse meningitis model, anti-CCL20 antibody treatment, CSF leukocyte counts, bacterial titer measurement, in vitro granulocyte chemotaxis assay PLOS ONE Medium 24699535
2023 TNFα activates TNFR1 (not TNFR2) in vascular cells to induce CCL20 expression post-ischemia, while simultaneously promoting CCR6 translocation to the cell surface of neutrophils. CCR6+ neutrophils expressing VEGF-A are proangiogenic; CCL20-CCR6 axis is required for their recruitment to ischemic sites. In diabetic mice with impaired revascularization, reduced proangiogenic neutrophil numbers correlated with diminished CCL20, and administration of recombinant CCL20 improved revascularization. Permanent femoral artery ligation mouse model, TNFR1/TNFR2 KO, bone marrow transplantation, flow cytometry, CCR6 surface translocation assay, recombinant CCL20 administration, laser Doppler imaging Circulation Research Medium 37641931
2020 CCR6 is abundantly expressed on human spermatozoa and CCL20 binds human sperm specifically (demonstrated by radioligand-binding assay). Cumulus granulosa cells and oocytes are a source of CCL20 with cycle-dependent peak expression in the preovulatory phase. CCL20 induces chemotactic responses of human sperm, and neutralization of CCL20 in follicular fluid significantly impairs sperm migratory responses. Radioligand-binding assay on human sperm, CCL20 immunostaining of ovarian tissue, CCL20 ELISA in follicular fluid, in vitro sperm chemotaxis assay with CCL20 neutralizing antibody Biology of Reproduction Medium 32412043
2017 CCN1/Cyr61 directly stimulates CCL20 production in keratinocytes via p38 and JNK signaling, enhancing AP-1 binding to the CCL20 promoter. This induction is independent of TNF-α, IL-22, and IL-17 pathways. In vivo, blocking or knockdown of CCN1 expression ameliorated skin inflammation and reduced CCL20 expression in imiquimod- and IL-23-induced psoriasis mouse models. Primary NHEK cultures, exogenous CCN1 protein stimulation, p38/JNK pharmacological inhibitors, ChIP (AP-1 binding at CCL20 promoter), CCN1 knockdown/blocking in mouse psoriasis models Journal of Dermatological Science Medium 28602508
2018 RIP4 (receptor-interacting protein kinase 4) directly interacts with STAT3 (identified by immunoprecipitation) and enhances STAT3 phosphorylation; transcriptional activation of STAT3 by RIP4 promotes CCL20 expression in keratinocytes in response to IL-17. IL-17 upregulates RIP4 mRNA and protein and activates the RIP4 promoter in HaCaT keratinocytes. HaCaT keratinocyte cell line, IL-17 stimulation, immunoprecipitation (RIP4–STAT3 interaction), STAT3 phosphorylation Western blot, microarray gene expression analysis Experimental Dermatology Medium 30044012
2009 Serum amyloid A (SAA) is a potent inducer of CCL20 secretion in rheumatoid arthritis synoviocytes, more potent than IL-1β, TNF-α, or IL-17A. SAA-induced CCL20 production requires NF-κB and partially JNK signaling; it is suppressed by dexamethasone or FK506. CCL20 production was not affected by polymyxin B pre-treatment, ruling out LPS contamination. RA synoviocyte primary cultures, ELISA, RT-PCR, NF-κB and JNK pharmacological inhibitors, dexamethasone/FK506 suppression Rheumatology Medium 19447772
2024 VDR (vitamin D receptor) binds directly to the CCL20 promoter and upregulates CCL20 transcription in pancreatic adenocarcinoma cells (demonstrated by ChIP and dual-luciferase reporter assay). VDR-driven CCL20 secretion promotes M2 macrophage polarization and recruitment; blocking CCL20 reversed VDR-mediated M2 macrophage polarization and recruitment in vitro and in vivo. ChIP (VDR binding at CCL20 promoter), dual-luciferase reporter assay, ELISA, M2 macrophage polarization assay, CCL20 neutralizing antibody, mouse xenograft model, flow cytometry Cell Communication and Signaling Medium 38600588
2024 CCR6 signaling in tumor-infiltrating regulatory T cells (Tregs) promotes glycolysis and lactic acid production, which is required for their immunosuppressive activity toward CD8+ T cells. Ccr6 ablation reduces Treg glycolysis, impairs Treg-mediated CD8+ T cell suppression, and improves survival across multiple tumor models; this benefit is abrogated by Treg or CD8+ T cell depletion. CCL20 siRNA knockdown also improved antitumor efficacy. Ccr6-/- mice (multiple tumor models), Treg/CD8+ T cell depletion, metabolic assays (glycolysis, lactate, glutamine), anti-PD-1 combination, siRNA CCL20 knockdown Cancer Immunology Research Medium 39133127
2022 SMAD4 loss in colon epithelial cells increases CCL20 expression and chemoattracts CCR6+ immune cells (Tregs, Th17, dendritic cells) into the colon, promoting colitis-associated carcinogenesis. CCR6 germline deletion in Smad4-conditional-KO mice abrogated these immune responses and significantly reduced colitis-associated tumor incidence, demonstrating that SMAD4 tumor suppressor function is mechanistically linked to suppression of CCL20-CCR6 signaling. Conditional colon-epithelial Smad4 KO mice crossed with Ccr6-/- mice, colitis-associated cancer model, histological tumor quantification, flow cytometry of immune infiltrates Gastroenterology Medium 35863523
2024 Lipid droplet (LD) accumulation in macrophages (LLMs) in hepatocellular carcinoma promotes CCL20 secretion; LDs prolong LLM survival and drive CCL20-mediated recruitment of CCR6+ Tregs. Mechanistically, tumor-induced triglyceride synthesis (via DGAT1/DGAT2) generates LDs in macrophages. Inhibiting DGAT1/DGAT2 significantly reduced Treg recruitment and delayed tumor growth in a mouse hepatic tumor model. Human HCC tissue analysis, macrophage LD induction experiments, DGAT1/DGAT2 pharmacological inhibition, CCL20 ELISA, Treg flow cytometry, mouse hepatic tumor model Cellular & Molecular Immunology Medium 38942796
2015 CCL20 and CCL19 (via CXCL8) enhance osteoclastogenesis indirectly through osteoblasts: CCL20 (500 pg/ml) increases osteoblast IL-6 production and proliferation (KI67, ALP mRNA), and conditioned medium from CCL20-treated osteoblasts enhances osteoclast formation. IL-6 inhibition reduces the stimulatory effect of CCL20-conditioned medium on osteoclast formation. CCL20 did not directly affect osteoclastogenesis. Primary human osteoblast cultures, CCL20 stimulation, IL-6 inhibitor, osteoclast precursor co-culture with conditioned medium, osteoclast counting PLOS ONE Medium 26103626
2015 CCL20 induces pro-inflammatory and matrix-degrading responses in cartilage: rhCCL20 increases mRNA expression of IL-6, COX-2, iNOS, MMP-13, ADAMTS-5, and collagen X in chondrocytes/cartilage explants, and increases release of MMP1/13, PGE2, proteoglycan fragments, and IL-6. It inhibits collagen type II mRNA expression. These effects indicate CCL20/CCR6 promotes an osteoarthritic catabolic phenotype. Human OA and donor chondrocyte/cartilage explant cultures, rhCCL20 stimulation, RT-PCR, ELISA, proteoglycan/GAG assay, immunohistochemistry Inflammation Research Medium 26189947
2022 CCL20 promotes endometriosis stromal cell (ESC) proliferation and migration via CCR6-mediated impairment of lysosomal function and blockade of autophagic flux (autolysosome degradation). CCR6 physically binds TFEB and inhibits its nuclear translocation, blocking TFEB-dependent autophagy. In vivo, CCL20-neutralizing antibody suppressed endometriosis lesion growth in mice. Co-IP (CCR6–TFEB binding), co-culture macrophage-ESC system, autophagic flux (mRFP-GFP-LC3 assay), lysosomal function assays (Lyso-tracker, Gal3, acid phosphatase), CCL20-neutralizing antibody in mouse endometriosis model Stem Cell Research & Therapy Medium 35841069

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 The CC chemokine CCL20 and its receptor CCR6. Cytokine & growth factor reviews 665 12948524
1997 Molecular cloning of a novel human CC chemokine liver and activation-regulated chemokine (LARC) expressed in liver. Chemotactic activity for lymphocytes and gene localization on chromosome 2. The Journal of biological chemistry 311 9038201
2021 Fusobacterium nucleatum promotes colorectal cancer metastasis through miR-1322/CCL20 axis and M2 polarization. Gut microbes 246 34632963
2020 The CCL20-CCR6 Axis in Cancer Progression. International journal of molecular sciences 214 32707869
2003 Airway epithelial cells release MIP-3alpha/CCL20 in response to cytokines and ambient particulate matter. American journal of respiratory cell and molecular biology 204 12760962
2019 Colorectal cancer cell-derived CCL20 recruits regulatory T cells to promote chemoresistance via FOXO1/CEBPB/NF-κB signaling. Journal for immunotherapy of cancer 187 31395078
2021 CCR6-CCL20 axis as a therapeutic target for autoimmune diseases. Autoimmunity reviews 184 33971346
1999 Selective expression of liver and activation-regulated chemokine (LARC) in intestinal epithelium in mice and humans. European journal of immunology 173 10064080
2004 Increased expression of CCL20 in human inflammatory bowel disease. Journal of clinical immunology 166 14997037
2001 Inducible expression of a CC chemokine liver- and activation-regulated chemokine (LARC)/macrophage inflammatory protein (MIP)-3 alpha/CCL20 by epidermal keratinocytes and its role in atopic dermatitis. International immunology 146 11133838
2006 CCR6 and CCL20: partners in intestinal immunity and lymphorganogenesis. Annals of the New York Academy of Sciences 137 17057190
2001 Neutrophils produce biologically active macrophage inflammatory protein-3alpha (MIP-3alpha)/CCL20 and MIP-3beta/CCL19. European journal of immunology 136 11449350
1999 Detection and localization of Mip-3alpha/LARC/Exodus, a macrophage proinflammatory chemokine, and its CCR6 receptor in human pancreatic cancer. International journal of cancer 131 10225458
2009 The chemokine CCL20 and its receptor CCR6 in human malignancy with focus on colorectal cancer. International journal of cancer 120 19480006
2011 CCL20, γδ T cells, and IL-22 in corneal epithelial healing. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 106 21518851
2023 PMN-MDSCs modulated by CCL20 from cancer cells promoted breast cancer cell stemness through CXCL2-CXCR2 pathway. Signal transduction and targeted therapy 103 36859354
2010 An immune paradox: how can the same chemokine axis regulate both immune tolerance and activation?: CCR6/CCL20: a chemokine axis balancing immunological tolerance and inflammation in autoimmune disease. BioEssays : news and reviews in molecular, cellular and developmental biology 101 20954179
2012 Regulation of CCL20 expression in astrocytes by IL-6 and IL-17. Glia 95 22319003
2019 Cisplatin-stimulated macrophages promote ovarian cancer migration via the CCL20-CCR6 axis. Cancer letters 89 31866467
2020 Structural basis for chemokine receptor CCR6 activation by the endogenous protein ligand CCL20. Nature communications 85 32541785
2022 CircSMARCC1 facilitates tumor progression by disrupting the crosstalk between prostate cancer cells and tumor-associated macrophages via miR-1322/CCL20/CCR6 signaling. Molecular cancer 83 36045408
2018 CCL20 triggered by chemotherapy hinders the therapeutic efficacy of breast cancer. PLoS biology 76 30052635
2019 The CCR6-CCL20 axis in humoral immunity and T-B cell immunobiology. Immunobiology 74 30772094
2018 CCL20 Expression by Tumor-Associated Macrophages Predicts Progression of Human Primary Cutaneous Melanoma. Cancer immunology research 74 29362221
2022 Identification and Molecular Characterization of Four New Blastocystis Subtypes Designated ST35-ST38. Microorganisms 70 36677338
2013 CCL20 induces migration and proliferation on breast epithelial cells. Journal of cellular physiology 68 23460117
2016 Tumor-associated macrophage-derived CCL20 enhances the growth and metastasis of pancreatic cancer. Acta biochimica et biophysica Sinica 67 27797715
2014 Transcriptional regulation of CCL20 expression. Microbes and infection 66 25130722
2016 Chemokine/chemokine receptor pair CCL20/CCR6 in human colorectal malignancy: An overview. World journal of gastroenterology 65 26811629
2024 Lipid droplet accumulation mediates macrophage survival and Treg recruitment via the CCL20/CCR6 axis in human hepatocellular carcinoma. Cellular & molecular immunology 64 38942796
2015 Antibiotic-resistant ST38, ST131 and ST405 strains are the leading uropathogenic Escherichia coli clones in Riyadh, Saudi Arabia. The Journal of antimicrobial chemotherapy 64 26183183
2018 Modulation of the CCR6-CCL20 Axis: A Potential Therapeutic Target in Inflammation and Cancer. Medicina (Kaunas, Lithuania) 62 30453514
2017 Human antigen R-regulated CCL20 contributes to osteolytic breast cancer bone metastasis. Scientific reports 58 28851919
2008 Exodus-1 (CCL20): evidence for the participation of this chemokine in spontaneous labor at term, preterm labor, and intrauterine infection. Journal of perinatal medicine 58 18576931
2005 Increase of CCL20 expression by human gingival fibroblasts upon stimulation with cytokines and bacterial endotoxin. Clinical and experimental immunology 58 16232215
2014 Syk mediates IL-17-induced CCL20 expression by targeting Act1-dependent K63-linked ubiquitination of TRAF6. The Journal of investigative dermatology 57 25202827
2018 Astrocyte-derived CCL20 reinforces HIF-1-mediated hypoxic responses in glioblastoma by stimulating the CCR6-NF-κB signaling pathway. Oncogene 56 29535421
2017 Protein engineering of the chemokine CCL20 prevents psoriasiform dermatitis in an IL-23-dependent murine model. Proceedings of the National Academy of Sciences of the United States of America 53 29109267
2020 CCL20 Signaling in the Tumor Microenvironment. Advances in experimental medicine and biology 50 32060846
2015 CrkL meditates CCL20/CCR6-induced EMT in gastric cancer. Cytokine 50 26044596
2014 CCR6 and CCL20: emerging players in the pathogenesis of rheumatoid arthritis. Immunology and cell biology 50 24394994
2014 CCR6, the sole receptor for the chemokine CCL20, promotes spontaneous intestinal tumorigenesis. PloS one 48 24866282
2007 Expression and role of CCR6/CCL20 chemokine axis in pulmonary sarcoidosis. Journal of leukocyte biology 47 17615381
2022 SMAD4 Suppresses Colitis-associated Carcinoma Through Inhibition of CCL20/CCR6-mediated Inflammation. Gastroenterology 43 35863523
2015 CCL20 is elevated during obesity and differentially regulated by NF-κB subunits in pancreatic β-cells. Biochimica et biophysica acta 42 25882704
2015 CCL20 and IL22 Messenger RNA Expression After Adalimumab vs Methotrexate Treatment of Psoriasis: A Randomized Clinical Trial. JAMA dermatology 42 25946554
2020 CCL20 in psoriasis: A potential biomarker of disease severity, inflammation, and impaired vascular health. Journal of the American Academy of Dermatology 41 33259876
2017 Role of CCL20 mediated immune cell recruitment in NF-κB mediated TRAIL resistance of pancreatic cancer. Biochimica et biophysica acta. Molecular cell research 41 28188806
2017 Role of CCL20/CCR6 and the ERK signaling pathway in lung adenocarcinoma. Oncology letters 41 29250193
2003 Expression of MIP-3alpha/CCL20, a macrophage inflammatory protein in oral squamous cell carcinoma. Archives of oral biology 41 12642237
2001 Genomic organization of the CC chemokine mip-3alpha/CCL20/larc/exodus/SCYA20, showing gene structure, splice variants, and chromosome localization. Genomics 41 11352563
2022 CCL20 promotes lung adenocarcinoma progression by driving epithelial-mesenchymal transition. International journal of biological sciences 40 35864953
2015 CXCL8 and CCL20 Enhance Osteoclastogenesis via Modulation of Cytokine Production by Human Primary Osteoblasts. PloS one 40 26103626
2007 Altered oscillator function affects clock resonance and is responsible for the reduced day-length sensitivity of CKB4 overexpressing plants. The Plant journal : for cell and molecular biology 40 17662034
2015 The relationship between CCR6 and its binding partners: does the CCR6-CCL20 axis have to be extended? Cytokine 37 25585877
2022 Inhibition of the CCR6-CCL20 axis prevents regulatory T cell recruitment and sensitizes head and neck squamous cell carcinoma to radiation therapy. Cancer immunology, immunotherapy : CII 36 36326893
2021 Single-cell sequencing unveils distinct immune microenvironments with CCR6-CCL20 crosstalk in human chronic pancreatitis. Gut 36 34702715
2011 Visfatin enhances CXCL8, CXCL10, and CCL20 production in human keratinocytes. Endocrinology 36 21673103
2008 Hypoxic synovial environment and expression of macrophage inflammatory protein 3gamma/CCL20 in juvenile idiopathic arthritis. Arthritis and rheumatism 36 18512817
2022 Plasma Olink Proteomics Identifies CCL20 as a Novel Predictive and Diagnostic Inflammatory Marker for Preeclampsia. Journal of proteome research 35 36301636
2013 miR-21 and its target gene CCL20 are both highly overexpressed in the microenvironment of colorectal tumors: significance of their regulation. Oncology reports 35 23817679
2008 Rho kinase-dependent CCL20 induced by dynamic compression of human chondrocytes. Arthritis and rheumatism 35 18759278
2017 CCR6/CCL20 chemokine axis in human immunodeficiency virus immunity and pathogenesis. The Journal of general virology 34 28005525
2014 Raloxifene suppresses experimental autoimmune encephalomyelitis and NF-κB-dependent CCL20 expression in reactive astrocytes. PloS one 34 24722370
2019 CCL20-CCR6 axis modulated traumatic brain injury-induced visual pathologies. Journal of neuroinflammation 33 31151410
2020 EGFR/Ras-induced CCL20 production modulates the tumour microenvironment. British journal of cancer 32 32601464
2016 CCL20/CCR6 promotes cell proliferation and metastasis in laryngeal cancer by activating p38 pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 32 27916417
2015 The chemokine CCL20 induces proinflammatory and matrix degradative responses in cartilage. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 32 26189947
2020 CCL20 is a novel ligand for the scavenging atypical chemokine receptor 4. Journal of leukocyte biology 31 32533638
2019 DEPDC1 drives hepatocellular carcinoma cell proliferation, invasion and angiogenesis by regulating the CCL20/CCR6 signaling pathway. Oncology reports 31 31322256
2018 CCL20 blockade increases the severity of nephrotoxic folic acid-induced acute kidney injury. The Journal of pathology 31 29984403
2020 EN2 as an oncogene promotes tumor progression via regulating CCL20 in colorectal cancer. Cell death & disease 30 32732864
2014 Leukocyte attraction by CCL20 and its receptor CCR6 in humans and mice with pneumococcal meningitis. PloS one 30 24699535
2024 Cathepsin D promotes polarization of tumor-associated macrophages and metastasis through TGFBI-CCL20 signaling. Experimental & molecular medicine 29 38297161
2017 Cyr61/CCN1 induces CCL20 production by keratinocyte via activating p38 and JNK/AP-1 pathway in psoriasis. Journal of dermatological science 26 28602508
2016 Disruption of CCL20-CCR6 interaction inhibits metastasis of advanced cutaneous T-cell lymphoma. Oncotarget 26 26789110
2020 Cross-border emergence of clonal lineages of ST38 Escherichia coli producing the OXA-48-like carbapenemase OXA-244 in Germany and Switzerland. International journal of antimicrobial agents 25 32919009
2008 Enhanced expression of CCL20 in human Helicobacter pylori-associated gastritis. Clinical immunology (Orlando, Fla.) 25 19006683
2021 Targeting the CCR6/CCL20 Axis in Entheseal and Cutaneous Inflammation. Arthritis & rheumatology (Hoboken, N.J.) 23 34081845
2024 VDR promotes pancreatic cancer progression in vivo by activating CCL20-mediated M2 polarization of tumor associated macrophage. Cell communication and signaling : CCS 22 38600588
2015 CCL20 and Beta-Defensin 2 Production by Human Lung Epithelial Cells and Macrophages in Response to Brucella abortus Infection. PloS one 22 26448160
2009 Phospholipase C, p38/MAPK, and NF-kappaB-mediated induction of MIP-3alpha/CCL20 by Porphyromonas gingivalis. Innate immunity 22 19710093
2024 RANKL/RANK signaling recruits Tregs via the CCL20-CCR6 pathway and promotes stemness and metastasis in colorectal cancer. Cell death & disease 21 38902257
2021 Salivary CCL20 Level as a Biomarker for Oral Squamous Cell Carcinoma. Cancer genomics & proteomics 21 33608307
2023 PPARδ dysregulation of CCL20/CCR6 axis promotes gastric adenocarcinoma carcinogenesis by remodeling gastric tumor microenvironment. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 20 37572185
2020 The EGFR-ERK/JNK-CCL20 Pathway in Scratched Keratinocytes May Underpin Koebnerization in Psoriasis Patients. International journal of molecular sciences 20 31936670
2020 Targeting CCL20 inhibits subarachnoid hemorrhage-related neuroinflammation in mice. Aging 20 32575072
2016 Macrophage Inflammatory Protein-3 Alpha (MIP-3α)/CCL20 in HIV-1-Infected Individuals. Journal of AIDS & clinical research 20 27617163
2009 Serum amyloid A protein stimulates CCL20 production in rheumatoid synoviocytes. Rheumatology (Oxford, England) 20 19447772
2009 CCL20/CCR6 chemokine/receptor expression in bone tissue from osteoarthritis and rheumatoid arthritis patients: different response of osteoblasts in the two groups. Journal of cellular physiology 20 19492413
2020 The Role of CCL20-CCR6 Axis in Ovarian Cancer Metastasis. OncoTargets and therapy 19 33335408
2019 CCL20 Promotes Ovarian Cancer Chemotherapy Resistance by Regulating ABCB1 Expression. Cell structure and function 19 30760665
2018 RIP4 upregulates CCL20 expression through STAT3 signalling in cultured keratinocytes. Experimental dermatology 19 30044012
2007 Helicobacter pylori induces CCL20 expression. Infection and immunity 19 17724069
2024 The CCR6-CCL20 Axis Promotes Regulatory T-cell Glycolysis and Immunosuppression in Tumors. Cancer immunology research 18 39133127
2022 CCL20/CCR6 axis mediates macrophages to promote proliferation and migration of ESCs by blocking autophagic flux in endometriosis. Stem cell research & therapy 18 35841069
2021 Indirubin attenuates IL-17A-induced CCL20 expression and production in keratinocytes through repressing TAK1 signaling pathway. International immunopharmacology 18 33611057
2019 Low prevalence of deficient mismatch repair (dMMR) protein in locally advanced rectal cancers (LARC) and treatment outcomes. Journal of gastrointestinal oncology 18 30788155
2023 Neutrophils for Revascularization Require Activation of CCR6 and CCL20 by TNFα. Circulation research 17 37641931
2020 CCL20-CCR6 axis directs sperm-oocyte interaction and its dysregulation correlates/associates with male infertility‡. Biology of reproduction 17 32412043

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