Affinage

IL20

Interleukin-20 · UniProt Q9NYY1

Audit flag: wrong gene
Length
176 aa
Mass
20.1 kDa
Annotated
2026-06-10
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL-20 is a pleiotropic IL-10-family cytokine that acts on epithelial, endothelial, and immune cells to coordinate inflammation, tissue remodeling, and barrier function, signaling through two distinct receptor complexes—a type I complex (IL-20Rα/IL-20Rβ) and a type II complex (IL-22R/IL-20Rβ)—both of which trigger STAT3 phosphorylation, while IL-20Rβ (IL-20R2) serves as the shared, immunoregulatory signaling subunit also engaged by IL-19 and IL-24 (PMID:11564763, PMID:19124723). It is produced chiefly by monocytes, dendritic cells, and keratinocytes in response to inflammatory stimuli, with IL-1β, TNF-α, IL-17A and IL-22 inducing keratinocyte IL-20, LPS driving expression through a MyD88–p38 MAPK pathway, and hypoxia inducing it via HIF-1α-bound promoter elements (PMID:19830738, PMID:17083366, PMID:16645593, PMID:15519673, PMID:19342680). Acting on keratinocytes, IL-20 drives acanthosis, induces psoriasis-associated proteins (S100A7, keratin 16) and antimicrobial genes, and sustains nuclear STAT3 activation, establishing it as a downstream effector of the IL-22→IL-20 cytokine cascade in epidermal pathology (PMID:17277128, PMID:19830738, PMID:18281438). Through IL-20R2, the IL-20 subfamily suppresses immune effector functions—dampening T-cell IFN-γ/IL-2 output, inhibiting actin-dependent neutrophil phagocytosis and migration, and limiting cutaneous IL-1β/IL-17A—thereby restraining antibacterial defense, as IL-20R2 loss heightens T-cell responses and receptor blockade improves S. aureus infection (PMID:19124723, PMID:28424238, PMID:23793061). In non-cutaneous tissues IL-20 activates endothelial JAK2/STAT5, ERK1/2, Akt, Rac/Rho and calcium signaling to promote arteriogenesis and lymphangiogenesis (PMID:17878297, PMID:19281830), activates hepatic stellate cells to drive TGF-β1-dependent liver fibrosis (PMID:24763901), promotes M1/M2 macrophage polarization, adipose inflammation and insulin resistance (PMID:34403503, PMID:32929072), and exerts dual epithelial roles in the gut—impairing the oesophageal barrier via MAPK/ERK1/2 downregulation of cornified-envelope proteins yet protecting against colitis by inducing STAT3 and suppressing IFN/STAT2-driven necroptosis (PMID:35613844, PMID:37884352). IL-20 transcription is controlled by an ERα/GATA3/FOXA1/ELL3 complex with KMT2B-mediated H3K4 methylation in breast cancer cells, and post-transcriptionally by HuR-mediated mRNA stabilization downstream of AMPK in psoriatic keratinocytes (PMID:27806114, PMID:28514748, PMID:26176762).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2001 High

    Established the receptor architecture of IL-20 signaling, defining how a single cytokine can act through two complexes and identifying STAT3 as the common output.

    Evidence Receptor binding, STAT3 phosphorylation, and STAT-reporter assays with multiple IL-20 subfamily ligands

    PMID:11564763

    Open questions at the time
    • Did not assign cell-type-specific receptor usage
    • Downstream gene programs from STAT3 not yet mapped
  2. 2003 Medium

    Showed IL-20 has a selective hematopoietic action, expanding the cytokine's biology beyond skin to multipotential progenitor regulation.

    Evidence CD34+ colony formation assays and IL-20 transgenic mice with cell-cycle analysis

    PMID:12855566

    Open questions at the time
    • Receptor and signaling mediating progenitor effect not defined
    • Physiological relevance to steady-state hematopoiesis unclear
  3. 2004 Medium

    Defined an upstream induction pathway, showing innate immune signals drive IL-20 transcription via a defined kinase cascade under negative glucocorticoid control.

    Evidence LPS stimulation of glial cells/macrophages, MyD88-deficient mice, p38 inhibition, dexamethasone treatment

    PMID:15519673

    Open questions at the time
    • Transcription factors downstream of p38 not identified
    • Findings in glia/macrophages may not generalize to keratinocytes
  4. 2006 Medium

    Identified the cellular sources of IL-20 and the inflammatory stimuli (IL-1β, TNF-α, integrin/adhesion, oxidized LDL, hypoxia) that induce it, while showing immune cells lack the receptor and act only as producers.

    Evidence qRT-PCR, flow cytometry, STAT assays, IHC of psoriatic skin, monocyte/endothelial stimulation, ApoE-/- atherosclerosis model

    PMID:16645593 PMID:16778121 PMID:17083366

    Open questions at the time
    • Relative contribution of keratinocyte vs myeloid sources in vivo not resolved
    • Mechanism linking oxidized LDL/hypoxia to transcription not yet defined here
  5. 2007 High

    Demonstrated IL-20 drives epidermal pathology and, separately, activates endothelial cells through a broad non-STAT3 signaling repertoire to promote arteriogenesis.

    Evidence Reconstituted human epidermis with microarray/IHC; endothelial signaling assays (JAK2/STAT5, ERK1/2, Akt, Rac/Rho, calcium), tube formation, rat hind-limb ischemia model

    PMID:17277128 PMID:17878297

    Open questions at the time
    • Receptor complex governing endothelial vs epithelial signaling not distinguished
    • Link between in vitro signaling and in vivo arteriogenesis indirect
  6. 2009 High

    Placed IL-20 within an IL-22-driven cytokine cascade, defined dendritic cells as producers and antimicrobial induction in keratinocytes, identified HIF-1α promoter control, lymphangiogenic signaling, and established IL-20R2 as an immunosuppressive subunit restraining T cells.

    Evidence Keratinocyte cytokine stimulation with neutralizing antibody; DC differentiation; luciferase/HIF-1α inhibition; lymphatic endothelial signaling with pharmacological inhibitors; IL-20R2 knockout mice with T-cell, DNA vaccination, and contact hypersensitivity assays

    PMID:18281438 PMID:19124723 PMID:19281830 PMID:19342680 PMID:19830738

    Open questions at the time
    • Whether IL-20R2 immunosuppression is cell-intrinsic to T cells not fully resolved
    • HIF-1α HRE occupancy shown by inhibition rather than direct binding
  7. 2012 Medium

    Extended IL-20 signaling to tumor cell invasion, linking MAPK/JAK-STAT activation to NF-κB/AP-1-driven MMP expression and migratory phenotypes.

    Evidence EMSA, immunoblot, RT-PCR, wound-healing/invasion assays in bladder cancer cell lines

    PMID:22962576

    Open questions at the time
    • No in vivo tumor model
    • Receptor complex used by bladder cells not defined
  8. 2013 High

    Revealed the host-detrimental side of IL-20 immunosuppression, showing the subfamily promotes S. aureus infection by suppressing cutaneous IL-1β/IL-17A, validating receptor blockade therapeutically.

    Evidence Murine S. aureus infection with cytokine/receptor-blockade, human keratinocyte stimulation, cytokine measurement

    PMID:23793061

    Open questions at the time
    • Cellular target of suppression in vivo not fully defined
    • Promoter genetics (rs1713239) link to expression only preliminary
  9. 2014 High

    Established IL-20 as a profibrotic driver in liver, acting on hepatic stellate cells through a TGF-β1 axis, with genetic and antibody loss-of-function confirming causality.

    Evidence In vitro HSC assays, CCl4 fibrosis model, anti-IL-20/anti-IL-20R1 antibodies, IL-20R1 knockout mice

    PMID:24763901

    Open questions at the time
    • Signaling pathway in HSCs not dissected
    • Receptor complex usage (type I vs II) in liver not specified
  10. 2015 Medium

    Defined transcriptional and post-transcriptional control of IL-20: an ERα/KMT2B-H3K4 methylation axis in breast cancer and AMPK-regulated HuR mRNA stabilization in psoriatic skin.

    Evidence ChIP, siRNA, proliferation/colony assays (breast cancer); RIP-seq, HuR immunofluorescence, in vivo AMPK inhibition (skin)

    PMID:26176762 PMID:27806114

    Open questions at the time
    • Connection between IL-20 transcript level and downstream pathology in breast cancer indirect
    • AMPK-HuR axis tested pharmacologically, not genetically
  11. 2016 Medium

    Validated soluble IL-20R2-Fc decoy as a therapeutic strategy that neutralizes all three subfamily cytokines, achieving anti-TNF-comparable efficacy in arthritis.

    Evidence In vitro binding/blockade assays, DBA/1 collagen-induced arthritis model, in situ ligand-receptor and colocalization analysis

    PMID:27619991

    Open questions at the time
    • Relative contribution of IL-20 vs IL-19/IL-24 not separated
    • Macrophage-intrinsic mechanism inferred from colocalization
  12. 2017 Medium

    Showed IL-20 directly disables activated neutrophils by inhibiting actin polymerization, providing a cellular mechanism for impaired antibacterial defense.

    Evidence Primary human neutrophil activation/migration assays, flow cytometry, actin polymerization, phagocytosis and exocytosis assays

    PMID:28424238

    Open questions at the time
    • Signaling pathway from receptor to actin not mapped
    • In vivo confirmation of neutrophil-specific effect lacking
  13. 2020 Medium

    Expanded IL-20 pathology to cardiac injury, adipose inflammation/insulin resistance, and pancreatic cancer, identifying it as a therapeutically tractable node including in combination with anti-PD-1.

    Evidence Cardiomyocyte H/R model with signaling readouts; adipocyte/macrophage assays and HFD model with anti-IL-20; KPC and orthotopic PDAC models with anti-IL-20/anti-PD-1

    PMID:31953216 PMID:32929072 PMID:34403503

    Open questions at the time
    • Receptor complex and STAT involvement vary and remain undefined across tissues
    • Tumor-cell vs stromal source of IL-20 not clarified
  14. 2022 High

    Resolved a dual epithelial role at gut barriers, with the subfamily impairing the oesophageal barrier via ERK1/2-driven loss of cornified-envelope proteins, contributing to eosinophilic esophagitis.

    Evidence Patient-derived organoids, RNA-seq, mass spectrometry, Il20R2 knockout EoE model, air-liquid interface cultures with ERK1/2 inhibition

    PMID:35613844

    Open questions at the time
    • Whether IL-20 alone or other subfamily members dominate not separated
    • Upstream inducer in EoE not defined
  15. 2024 High

    Identified a protective epithelial function for IL-20 in colitis, where STAT3 induction suppresses IFN/STAT2-driven necroptosis, contrasting with its pathogenic roles elsewhere.

    Evidence Il20 and Il20rb knockout mice, DSS colitis, IEC organoids, RNA-seq, Co-IP, RNAScope, recombinant IL-20 rescue

    PMID:37884352

    Open questions at the time
    • Molecular basis of IFN/STAT2 suppression by STAT3 not fully resolved
    • Cellular source of protective IL-20 in colon not pinpointed

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how IL-20 selects between type I and type II receptor complexes and between STAT3 and the alternative (JAK2/STAT5, ERK, Akt, PKC/NADPH) signaling branches to produce opposite outcomes—protective versus pathogenic—across tissues.
  • No structural or quantitative model linking receptor stoichiometry to signaling branch choice
  • Determinants of context-dependent pro- vs anti-inflammatory output unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0098772 molecular function regulator activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-1266738 Developmental Biology 3
Partners
IL20RAIL20RBIL22RA1

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 IL-20 signals through two distinct receptor complexes: a type I complex (IL-20Rα/IL-20Rβ) and a type II complex (IL-22R/IL-20Rβ). Both receptor complexes, upon ligand binding, induce STAT3 phosphorylation and activation of STAT-binding site promoters. IL-19 signals only through the type I complex, while mda-7/IL-24 signals through both. Receptor binding assays, STAT3 phosphorylation assays, reporter gene (minimal promoter with STAT-binding sites) Journal of immunology (Baltimore, Md. : 1950) High 11564763
2007 IL-20 induces acanthosis, expression of psoriasis-associated proteins S100A7 and keratin 16, and persistent nuclear STAT3 activation in reconstituted human epidermis (RHE). Gene expression analysis showed IL-20 regulates inflammatory response genes, wound healing, and keratinocyte differentiation markers. Reconstituted human epidermis (RHE) model, gene expression microarray, immunohistochemistry Journal of immunology (Baltimore, Md. : 1950) High 17277128
2009 IL-22 induces IL-20 mRNA and protein production in human keratinocytes, establishing a cytokine cascade. Some IL-22 effects on differentiation-regulating genes were partially mediated by endogenous secreted IL-20, as demonstrated by partial attenuation with anti-IL-20 antibody. IL-17A and TNF-α also induced IL-20 in keratinocytes, but IFN-γ and IL-20 itself did not regulate IL-20 expression. Keratinocyte culture with cytokine stimulation, RT-PCR, ELISA, neutralizing antibody blockade European journal of immunology Medium 19830738
2006 IL-20 is produced by monocytes and keratinocytes. In keratinocytes, IL-1β increases IL-20 expression approximately 10-fold. Neither receptor complex for IL-20 (IL-20R1/IL-20R2 nor IL-22R1/IL-20R2) is expressed on immune cells, and IL-20 does not activate STAT molecules in immune cells. IFN-γ decreases IL-20R1 expression and increases IL-22R1 expression on keratinocytes. Quantitative RT-PCR, STAT activation assays, flow cytometry, in vitro stimulation Experimental dermatology Medium 17083366
2006 IL-20 expression in psoriatic skin is predominantly from CD68+/CD11c+ myeloid-derived dermal leukocytes (monocytes), not keratinocytes. In vitro, plastic adhesion, β2 integrin activation, and TNF-α stimulate IL-20 expression in monocytes. IL-20 treatment of keratinocytes upregulates IFN-γ-induced and disease-related genes as assessed by microarray. Immunohistochemistry, in vitro monocyte stimulation, microarray of IL-20-treated keratinocytes The Journal of investigative dermatology Medium 16645593
2006 IL-20 promotes atherosclerosis in apolipoprotein E-deficient mice when delivered via intramuscular electroporation of expression vector. IL-20 upregulates CXCL9 and CXCL11 transcripts in human umbilical vein endothelial cells. IL-20 transcripts increase in hypoxic monocytes and monocytes treated with oxidized LDL. In vivo IL-20 expression vector delivery in ApoE-/- mice, in vitro endothelial cell stimulation, RT-PCR Arteriosclerosis, thrombosis, and vascular biology Medium 16778121
2007 IL-20 promotes arteriogenesis and improves blood perfusion in a rat ischemic hind-limb model. In endothelial cells, IL-20 activates JAK2/STAT5, Erk1/2, and Akt phosphorylation; activates small GTP-binding proteins Rac and Rho; induces intracellular calcium release; and promotes tube formation without affecting endothelial cell proliferation or motility. In vitro endothelial cell signaling assays, tube formation assay, in vivo rat hind-limb ischemia model with IL-20 delivery Proceedings of the National Academy of Sciences of the United States of America High 17878297
2009 Maturing dendritic cells (DCs) produce IL-20 in response to bacterial stimuli and inflammatory cytokines. In keratinocytes, IL-20 induces expression of antimicrobial proteins. Combining IL-20 and IL-29 resulted in a stronger response to TLR2 and TLR3 activation in keratinocytes than either cytokine alone. Monocyte/DC differentiation in vitro, RT-PCR, co-stimulation assays in keratinocytes Journal of leukocyte biology Medium 18281438
2009 IL-20R2-deficient CD8+ and CD4+ T cells show significantly elevated IFN-γ and IL-2 secretion upon stimulation with Con A or anti-CD3/CD28, while IL-10 secretion by activated CD4+ IL-20R2-/- cells is diminished. IL-20R2 knockout mice develop more antigen-specific CD8+ and CD4+ IFN-γ+ T cells after DNA vaccination and show increased sensitivity in a contact hypersensitivity model, demonstrating that IL-20R2 signaling (by IL-19, IL-20, IL-24) directly down-regulates T cell responses in vitro and in vivo. IL-20R2 knockout mouse generation, in vitro T cell stimulation, DNA vaccination model, contact hypersensitivity model Journal of immunology (Baltimore, Md. : 1950) High 19124723
2009 IL-20 activates lymphatic endothelial cells (hTERT-HDLEC) causing increased intracellular calcium, Akt and eNOS phosphorylation (via PI3K/Akt), NO production, ERK1/2 and mTOR phosphorylation, actin polymerization, tube formation (PI3K- and mTOR-dependent), and cell migration comparable to VEGF-C. ERK1/2 pathway mediates IL-20-induced proliferation. Calcium imaging, Western blotting for phosphorylated signaling intermediates, pharmacological inhibitors (wortmannin, rapamycin, PD98059), tube formation and sprouting assays in lymphatic endothelial cells Microvascular research Medium 19281830
2009 IL-20 is regulated by hypoxia-inducible factor-1α (HIF-1α): two putative hypoxia response elements (HREs) in the human IL20 gene promoter were identified, and HIF-1α inhibition blocked CoCl2-induced IL-20 expression. IL-20 activates JAK2/STAT3 and ERK1/2 signaling in glioblastoma cells and induces their proliferation and production of IL-1β, IL-8, and MCP-1. Promoter activity (luciferase reporter), HIF-1α inhibitor treatment, signaling assays (JAK2/STAT3, ERK1/2 phosphorylation), in vitro proliferation assays Journal of immunology (Baltimore, Md. : 1950) Medium 19342680
2013 IL-19, IL-20, and IL-24 signaling through type I and type II IL-20 receptors suppresses cutaneous IL-1β and IL-17A production, thereby promoting S. aureus infection in mice. Antibody blockade of the IL-20 receptor improved infection outcomes in mice. Similar immunosuppressive effects were observed in human keratinocytes exposed to S. aureus. In vivo murine S. aureus infection model with cytokine treatment or receptor blockade, in vitro human keratinocyte stimulation, cytokine measurement Nature immunology High 23793061
2014 IL-20 activates hepatic stellate cells (HSCs) and upregulates TGF-β1 expression. IL-20 increases TGF-β1, TNF-α, and type I collagen expression and promotes proliferation and migration of activated HSCs. Anti-IL-20 monoclonal antibody and anti-IL-20R1 monoclonal antibody attenuate CCl4-induced liver fibrosis in mice. IL-20R1-deficient mice are protected from liver injury. In vitro HSC activation assays, CCl4 mouse model of liver fibrosis, monoclonal antibody treatment, IL-20R1 knockout mice, ELISA, histology Hepatology (Baltimore, Md.) High 24763901
2015 IL-20 expression in MCF-7 breast cancer cells is transcriptionally induced by estradiol (E2) through estrogen receptor α (ERα)-mediated recruitment of the histone methyltransferase KMT2B to the IL-20 promoter, leading to H3K4 methylation. Depletion of KMT2B or IL-20 disrupts estrogen signaling, attenuates cell proliferation, reduces colony formation, and causes cell cycle arrest. ChIP assay for histone methylation and transcription factor binding, siRNA knockdown of KMT2B and IL-20, cell proliferation and colony formation assays PloS one Medium 27806114
2015 IL-20 post-transcriptional regulation in psoriatic skin involves the RNA-binding protein HuR, which relocalizes from the nucleus to the cytoplasm in psoriatic keratinocytes to stabilize IL-20 mRNA. AMPK activity is impaired in psoriatic epidermis and is responsible for HuR cytoplasmic relocalization. In vivo AMPK inhibition in mouse epidermis promotes HuR cytoplasmic localization and IL-20 overproduction with accompanying acanthosis and hyperkeratosis. Ribonucleoprotein immunoprecipitation with high-throughput sequencing (RIP-seq), immunofluorescence for HuR localization, in vivo pharmacological AMPK inhibition in mice, histology The Journal of investigative dermatology Medium 26176762
2017 IL-20 directly targets activated human neutrophils: upon migration and activation (mimicking S. aureus infection conditions), neutrophils alter expression of IL-20 receptor chains and become responsive to IL-20, which inhibits actin polymerization and actin-dependent functions including phagocytosis, granule exocytosis, and migration. In vitro neutrophil activation/migration assays, flow cytometry for receptor expression, actin polymerization assays, phagocytosis and granule exocytosis assays Journal of immunology (Baltimore, Md. : 1950) Medium 28424238
2017 A transcriptional complex composed of ERα, GATA3, FOXA1, and ELL3 regulates IL-20 expression in ER+ breast cancer cells. ELL3 associates with ERα to increase its binding affinity to the IL-20 promoter and may prevent FOXA1 (a repressor) from binding the same region. GATA3 and ERα activate IL-20 expression while FOXA1 represses it. ChIP assays, co-immunoprecipitation, siRNA knockdown, promoter reporter assays Oncotarget Medium 28514748
2020 IL-20 promotes cardiomyocyte apoptosis during hypoxia/reoxygenation (H/R) by activating the PKC/NADPH oxidase pathway, leading to increased Ca2+, elevated oxidative stress, and downregulation of AKT. Anti-IL-20 treatment reduced cardiomyocyte apoptosis in the H/R model. In vitro H9C2 and primary cardiomyocyte H/R model, Western blotting for signaling intermediates, viability assays, pharmacological inhibition Biochimica et biophysica acta. Molecular basis of disease Medium 31953216
2020 IL-20 regulates adipocyte differentiation and promotes polarization of bone marrow-derived macrophages toward proinflammatory M1 type. IL-20 causes inflammation and macrophage retention in adipose tissues by upregulating TNF-α, MCP-1, netrin 1, and unc5b in macrophages and netrin 1, leptin, and MCP-1 in adipocytes. IL-20 promotes insulin resistance by inhibiting glucose uptake in mature adipocytes through the SOCS-3 pathway. In vitro adipocyte differentiation and macrophage polarization assays, Western blotting, ELISA, glucose uptake assays, in vivo HFD mouse model with anti-IL-20 antibody treatment Immunology Medium 34403503
2022 IL-20 subfamily cytokines (IL-19, IL-20, IL-24) impair the oesophageal epithelial barrier by downregulating filaggrins and other cornified envelope proteins via the MAPK/ERK1/2 pathway. Il20R2-/- animals show reduced eosinophil infiltration, lower Th2 cytokine expression, and preserved filaggrin expression in experimental EoE. ERK1/2 blockade prevents epithelial barrier impairment in patient-derived air-liquid interface cultures and attenuates experimental EoE. Patient-derived oesophageal organoids, RNA-seq, mass spectrometry, Il20R2 knockout EoE mouse model, air-liquid interface cultures with ERK1/2 inhibition Gut High 35613844
2024 IL-20 controls resolution of experimental colitis by inducing STAT3 and suppressing IFN/STAT2 signaling in intestinal epithelial cells (IECs). IL-20 deficiency or IL-20Rb deficiency increases IFN/STAT2 activity and susceptibility to DSS-induced colitis. IL-20 blocks IFN/STAT2-induced necroptotic cell death in IEC-derived organoids. Epithelial STAT2 deletion (Stat2 knockout in IECs) reduces colitis susceptibility, and IL-20 administration suppresses colitis in wild-type animals. Il20 and Il20rb knockout mice, DSS colitis model, IEC-derived 3D organoids, RNA-seq, Western blot, co-immunoprecipitation, confocal microscopy, RNAScope, recombinant IL-20 administration Gut High 37884352
2003 IL-20 selectively enhances colony formation by CD34+ multipotential hematopoietic progenitors in vitro, with no effect on erythroid, granulocyte-macrophage, or megakaryocyte progenitors. IL-20 transgenic mice show increased numbers and cell cycling of multipotential (but not other) progenitors in vivo. In vitro colony formation assays with CD34+ progenitors, IL-20 transgenic mouse model, cell cycle analysis Blood Medium 12855566
2004 LPS induces IL-20 expression in primary murine glial cells and RAW264.7 macrophages through a MyD88-p38 MAPK-dependent signaling pathway, independent of de novo protein synthesis. Dexamethasone inhibits LPS-induced IL-20 expression, indicating negative glucocorticoid feedback regulation. Primary glial cell culture with LPS, MyD88-deficient mice, pharmacological inhibitor (SB203580 for p38), protein synthesis inhibitors, RT-PCR Brain research. Molecular brain research Medium 15519673
2016 In collagen-induced arthritis (CIA), recombinant human soluble IL-20R2-Fc fusion protein blocks signaling of IL-19, IL-20, and IL-24 with high affinity in vitro and achieves efficacy comparable to etanercept in established arthritis. In situ analysis shows IL-20 subfamily cytokines and TNFR signals converge in macrophages within inflamed tissues. In vitro receptor binding assays, signaling blockade assays, DBA/1 mouse CIA model with IL-20R2-Fc treatment, in situ ligand-receptor functional binding analysis, colocalization immunostaining Journal of immunology (Baltimore, Md. : 1950) Medium 27619991
2020 IL-20 promotes tumor growth and M2-like macrophage polarization in pancreatic ductal adenocarcinoma (PDAC) models, and targeting IL-20 with anti-IL-20 monoclonal antibody (7E) attenuates PD-L1 expression on tumor cells. Combination of anti-IL-20 and anti-PD-1 antibodies shows better efficacy in inhibiting tumor growth than either alone in an orthotopic PDAC model. KPC transgenic mouse model, orthotopic PDAC mouse model, anti-IL-20 monoclonal antibody treatment, combination antibody therapy, tumor analysis Nature communications Medium 32929072
2022 In grass carp, IL-20R2 (CRFB16) binds IL-20 by co-immunoprecipitation, while IL-20R1 (CRFB8) does not bind IL-20 but is responsible for activating STAT3 phosphorylation. Structural modeling shows that key residues involved in IL-20/receptor interaction are conserved between grass carp and humans. Co-immunoprecipitation, STAT3 phosphorylation assays, structural modeling Fish & shellfish immunology Low 36414129
2012 IL-20 stimulation of bladder cancer cells upregulates MMP-2 and MMP-9 expression, activates transcription factors NF-κB and AP-1 (regulating the MMP-9 promoter), and activates MAPK and JAK-STAT signaling, thereby enhancing wound-healing migration and invasion capacity. EMSA, immunoblot, real-time PCR, wound-healing/invasion assays, confocal immunofluorescence in bladder cancer cell lines PloS one Medium 22962576
2013 IL-20 promoter activity is synergistically enhanced by bacterial-like DNA (CpG-A) or IL-1β in combination with the risk-associated G allele at SNP rs1713239 in the IL-20 promoter region. Increased IL-20 expression was observed in psoriatic lesional skin of patients carrying the risk G allele upon stimulation. Luciferase reporter gene assays with allele-specific constructs, stimulation with CpG-A and IL-1β, patient sample analysis The Journal of investigative dermatology Low 23892591

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 The effects of IL-20 subfamily cytokines on reconstituted human epidermis suggest potential roles in cutaneous innate defense and pathogenic adaptive immunity in psoriasis. Journal of immunology (Baltimore, Md. : 1950) 422 17277128
2009 IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-gamma are not. Journal of molecular medicine (Berlin, Germany) 354 19330474
2001 Cutting edge: STAT activation by IL-19, IL-20 and mda-7 through IL-20 receptor complexes of two types. Journal of immunology (Baltimore, Md. : 1950) 340 11564763
2014 The IL-20 subfamily of cytokines--from host defence to tissue homeostasis. Nature reviews. Immunology 318 25421700
2008 The extended IL-10 superfamily: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29. The Journal of allergy and clinical immunology 257 18405958
2006 Interleukin (IL)-19, IL-20 and IL-24 are produced by and act on keratinocytes and are distinct from classical ILs. Experimental dermatology 205 17083366
2004 Cutting edge: IL-26 signals through a novel receptor complex composed of IL-20 receptor 1 and IL-10 receptor 2. Journal of immunology (Baltimore, Md. : 1950) 146 14764663
2009 The Th17 cytokine IL-22 induces IL-20 production in keratinocytes: a novel immunological cascade with potential relevance in psoriasis. European journal of immunology 144 19830738
2008 Maturing dendritic cells are an important source of IL-29 and IL-20 that may cooperatively increase the innate immunity of keratinocytes. Journal of leukocyte biology 131 18281438
2006 Regulation of T cells and cytokines by the interleukin-10 (IL-10)-family cytokines IL-19, IL-20, IL-22, IL-24 and IL-26. European journal of immunology 124 16365913
2013 Signaling via the IL-20 receptor inhibits cutaneous production of IL-1β and IL-17A to promote infection with methicillin-resistant Staphylococcus aureus. Nature immunology 107 23793061
2007 IL-19 and IL-20: two novel cytokines with importance in inflammatory diseases. Expert opinion on therapeutic targets 99 17465720
2004 Bystander activity of Ad-mda7: human MDA-7 protein kills melanoma cells via an IL-20 receptor-dependent but STAT3-independent mechanism. Molecular therapy : the journal of the American Society of Gene Therapy 93 15564140
2007 The expression of IL-20 and IL-24 and their shared receptors are increased in rheumatoid arthritis and spondyloarthropathy. Cytokine 92 18061474
2005 Detection of IL-20 and its receptors on psoriatic skin. Clinical immunology (Orlando, Fla.) 91 16043414
2009 IL-17 and IL-22 mediate IL-20 subfamily cytokine production in cultured keratinocytes via increased IL-22 receptor expression. European journal of immunology 85 19731362
2006 Prominent production of IL-20 by CD68+/CD11c+ myeloid-derived cells in psoriasis: Gene regulation and cellular effects. The Journal of investigative dermatology 84 16645593
2006 IL-20 is expressed in atherosclerosis plaques and promotes atherosclerosis in apolipoprotein E-deficient mice. Arteriosclerosis, thrombosis, and vascular biology 78 16778121
2010 IL-24 transgenic mice: in vivo evidence of overlapping functions for IL-20, IL-22, and IL-24 in the epidermis. Journal of immunology (Baltimore, Md. : 1950) 77 20061404
2017 IL-22R Ligands IL-20, IL-22, and IL-24 Promote Wound Healing in Diabetic db/db Mice. PloS one 74 28125663
2003 IL-10 subfamily members: IL-19, IL-20, IL-22, IL-24 and IL-26. Immunology letters 72 12941475
2006 IL-20: biological functions and clinical implications. Journal of biomedical science 70 16703417
2014 IL-20 and IL-20R1 antibodies protect against liver fibrosis. Hepatology (Baltimore, Md.) 65 24763901
2018 IL-20 receptor cytokines in autoimmune diseases. Journal of leukocyte biology 63 30260500
2009 IL-20 is regulated by hypoxia-inducible factor and up-regulated after experimental ischemic stroke. Journal of immunology (Baltimore, Md. : 1950) 63 19342680
2020 IL-20 antagonist suppresses PD-L1 expression and prolongs survival in pancreatic cancer models. Nature communications 60 32929072
2005 mda-7/IL24 kills pancreatic cancer cells by inhibition of the Wnt/PI3K signaling pathways: identification of IL-20 receptor-mediated bystander activity against pancreatic cancer. Molecular therapy : the journal of the American Society of Gene Therapy 60 15851011
2018 The IL-20 Cytokine Family in Rheumatoid Arthritis and Spondyloarthritis. Frontiers in immunology 59 30319661
2006 Human interleukin 24 (MDA-7/IL-24) protein kills breast cancer cells via the IL-20 receptor and is antagonized by IL-10. Cancer immunology, immunotherapy : CII 58 16710719
2010 IL-20: biological functions mediated through two types of receptor complexes. Cytokine & growth factor reviews 55 20864382
2007 Association analysis of IL19, IL20 and IL24 genes in palmoplantar pustulosis. The British journal of dermatology 55 17263806
2007 IL-20 is an arteriogenic cytokine that remodels collateral networks and improves functions of ischemic hind limbs. Proceedings of the National Academy of Sciences of the United States of America 55 17878297
2012 Identification of pro-inflammatory cytokines associated with muscle invasive bladder cancer; the roles of IL-5, IL-20, and IL-28A. PloS one 53 22962576
2009 IL-20 receptor 2 signaling down-regulates antigen-specific T cell responses. Journal of immunology (Baltimore, Md. : 1950) 53 19124723
2005 Possible relations between the polymorphisms of the cytokines IL-19, IL-20 and IL-24 and plaque-type psoriasis. Genes and immunity 53 15889129
2011 Research in practice: IL-22 and IL-20: significance for epithelial homeostasis and psoriasis pathogenesis. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG 52 21251229
2010 IL-19, IL-20 and IL-24: potential therapeutic targets for autoimmune diseases. Expert opinion on therapeutic targets 50 21073280
2008 IL-20 may contribute to the pathogenesis of human intervertebral disc herniation. Spine 42 18758357
2019 Interleukin (IL)-22 from IL-20 Subfamily of Cytokines Induces Colonic Epithelial Cell Proliferation Predominantly through ERK1/2 Pathway. International journal of molecular sciences 41 31311100
2018 IL-19 and Other IL-20 Family Member Cytokines in Vascular Inflammatory Diseases. Frontiers in immunology 41 29681905
2008 Evaluation of IL10, IL19 and IL20 gene polymorphisms and chronic hepatitis B infection outcome. International journal of immunogenetics 41 18479293
2003 Selective enhancement of multipotential hematopoietic progenitors in vitro and in vivo by IL-20. Blood 38 12855566
2022 IL-20 subfamily cytokines impair the oesophageal epithelial barrier by diminishing filaggrin in eosinophilic oesophagitis. Gut 37 35613844
2016 IL-20 promotes epithelial healing of the injured mouse cornea. Experimental eye research 35 27818315
2011 IL-20 is epigenetically regulated in NSCLC and down regulates the expression of VEGF. European journal of cancer (Oxford, England : 1990) 35 21565488
2005 IL-20, an anti-angiogenic cytokine that inhibits COX-2 expression. Biochemical and biophysical research communications 35 15950941
2006 Leukocyte infiltration and mRNA expression of IL-20, IL-8 and TNF-R P60 in psoriatic skin is driven by TNF-alpha. International journal of immunopathology and pharmacology 34 16831294
2009 IL-20 activates human lymphatic endothelial cells causing cell signalling and tube formation. Microvascular research 31 19281830
2013 IL-20, IL-21 and p40: potential biomarkers of treatment response for ustekinumab. Acta dermato-venereologica 30 22930279
2012 Etanercept suppresses regenerative hyperplasia in psoriasis by acutely downregulating epidermal expression of interleukin (IL)-19, IL-20 and IL-24. The British journal of dermatology 30 22458549
2020 IL-20 in Acute Kidney Injury: Role in Pathogenesis and Potential as a Therapeutic Target. International journal of molecular sciences 28 32028746
2016 Diabetic Wounds Exhibit Decreased Ym1 and Arginase Expression with Increased Expression of IL-17 and IL-20. Advances in wound care 28 27867753
2017 Increased interleukin (IL)-20 and IL-24 target osteoblasts and synovial monocytes in spondyloarthritis. Clinical and experimental immunology 26 28369789
2024 IL-20 controls resolution of experimental colitis by regulating epithelial IFN/STAT2 signalling. Gut 25 37884352
2021 IL-20 is involved in obesity by modulation of adipogenesis and macrophage dysregulation. Immunology 24 34403503
2011 IL10 family member genes IL19 and IL20 are associated with recurrent wheeze after respiratory syncytial virus bronchiolitis. Pediatric research 24 21814157
2006 The murine liver is a potential target organ for IL-19, IL-20 and IL-24: Type I Interferons and LPS regulate the expression of IL-20R2. Journal of hepatology 24 17069926
2016 A Broad Blockade of Signaling from the IL-20 Family of Cytokines Potently Attenuates Collagen-Induced Arthritis. Journal of immunology (Baltimore, Md. : 1950) 23 27619991
2018 The roles of IL-19 and IL-20 in the inflammation of degenerative lumbar spondylolisthesis. Journal of inflammation (London, England) 22 30250404
2016 Regulation of IL-20 Expression by Estradiol through KMT2B-Mediated Epigenetic Modification. PloS one 22 27806114
2012 Expression of IL-20 in synovium and lesional skin of patients with psoriatic arthritis: differential response to alefacept treatment. Arthritis research & therapy 21 23006144
2017 IL-20 Signaling in Activated Human Neutrophils Inhibits Neutrophil Migration and Function. Journal of immunology (Baltimore, Md. : 1950) 20 28424238
2015 IL-20 in rheumatoid arthritis. Drug discovery today 20 26297177
2020 Effects of IL-1β, IL-20, and BMP-2 on Intervertebral Disc Inflammation under Hypoxia. Journal of clinical medicine 19 31947928
2006 Human fetal membrane expression of IL-19 and IL-20 and its differential effect on inflammatory cytokine production. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 19 16854693
2003 IL-20: a new target for the treatment of inflammatory skin disease. Expert opinion on therapeutic targets 18 12667095
2018 Modulation of Th1/Tc1 and Th17/Tc17 responses in pulmonary tuberculosis by IL-20 subfamily of cytokines. Cytokine 17 29684756
2004 Bacterial endotoxin induces IL-20 expression in the glial cells. Brain research. Molecular brain research 17 15519673
2022 IL-20 promotes cutaneous inflammation and peripheral itch sensation in atopic dermatitis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16 35486004
2016 The Role of the IL-20 Subfamily in Glaucoma. Mediators of inflammation 16 26903709
2015 AMPK/HuR-Driven IL-20 Post-Transcriptional Regulation in Psoriatic Skin. The Journal of investigative dermatology 16 26176762
2021 Expression of IL-20 Receptor Subunit β Is Linked to EAE Neuropathology and CNS Neuroinflammation. Frontiers in cellular neuroscience 15 34557075
2020 IL-20 promotes hypoxia/reoxygenation-induced mitochondrial dysfunction and apoptosis in cardiomyocytes by upregulating oxidative stress by activating the PKC/NADPH oxidase pathway. Biochimica et biophysica acta. Molecular basis of disease 15 31953216
2020 A single-center observational study on the expression of circulating interleukin-20 levels and predicting outcomes in human chronic heart failure: A 2-year follow-up cohort study: Higher IL-20 levels suggest poorer outcomes in CHF patients. Clinica chimica acta; international journal of clinical chemistry 14 32622964
2018 Cetacea are natural knockouts for IL20. Immunogenetics 14 29998404
2012 Combination of IL-1 receptor antagonist, IL-20 and CD40 ligand for the prediction of acute cellular renal allograft rejection. Journal of clinical immunology 14 22948742
2012 Genetic polymorphisms of interleukin 20 (IL-20) in patients with ulcerative colitis. Immunology letters 12 23183096
2018 The IL20 Genetic Polymorphism Is Associated with Altered Clinical Outcome in Septic Shock. Journal of innate immunity 10 29334679
2019 Murine astrocytes are responsive to the pro-inflammatory effects of IL-20. Neuroscience letters 9 31238130
2017 A transcriptional complex composed of ER(α), GATA3, FOXA1 and ELL3 regulates IL-20 expression in breast cancer cells. Oncotarget 9 28514748
2015 Neutralizing Anti-IL20 Antibody Treatment Significantly Modulates Low Grade Inflammation without Affecting HbA1c in Type 2 Diabetic db/db Mice. PloS one 9 26162095
2021 IL-20 Cytokines Are Involved in Epithelial Lesions Associated with Virus-Induced COPD Exacerbation in Mice. Biomedicines 8 34944654
2014 Reduction of IL-20 Expression in Rheumatoid Arthritis by Linear Polarized Infrared Light Irradiation. Laser therapy 8 25071309
2014 The correlation between IL-20 and the Th2 immune response in human asthma. Asian Pacific journal of allergy and immunology 8 25543042
2021 TNFα inhibitors reduce bone loss in rheumatoid arthritis independent of clinical response by reducing osteoclast precursors and IL-20. Rheumatology (Oxford, England) 7 32984900
2023 IL-20 Cytokines Are Involved in the Repair of Airway Epithelial Barrier: Implication in Exposure to Cigarette Smoke and in COPD Pathology. Cells 6 37887308
2022 Grass carp IL-20 binds to IL-20R2 but induces STAT3 phosphorylation via IL-20R1. Fish & shellfish immunology 6 36414129
2022 IL-20 Activates ERK1/2 and Suppresses Splicing of X-Box Protein-1 in Intestinal Epithelial Cells but Does Not Improve Pathology in Acute or Chronic Models of Colitis. International journal of molecular sciences 6 36613621
2016 The IL-20 receptor axis in immune-mediated inflammatory arthritis: novel links between innate immune recognition and bone homeostasis. Scandinavian journal of rheumatology 6 27687482
2015 Interleukins (ILs), a fascinating family of cytokines. Part II: ILs from IL-20 to IL-38. Theoretical biology forum 6 27167908
2025 Unraveling the role of the IL-20 cytokine family in neurodegenerative diseases: Mechanisms and therapeutic insights. International immunopharmacology 5 40068518
2023 Manipulation of osteogenic and adipogenic differentiation of human degenerative disc and ligamentum flavum derived progenitor cells using IL-1β, IL-19, and IL-20. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 5 37563485
2022 The IL-20RB receptor and the IL-20 signaling pathway in regulating host defense in oral mucosal candidiasis. Frontiers in cellular and infection microbiology 5 36225230
2020 Common Variants in IL-20 Gene are Associated with Subclinical Atherosclerosis, Cardiovascular Risk Factors and IL-20 Levels in the Cohort of the Genetics of Atherosclerotic Disease (GEA) Mexican Study. Biomolecules 5 31947776
2017 IL-20 contributes to low grade inflammation and weight gain in the Psammomys obesus. International immunopharmacology 5 28187313
2019 Correlation Between IL-20 and De Quervain's Disease Severity. Annals of plastic surgery 4 30540601
2025 Rational Identification of Ritonavir as IL-20 Receptor A Ligand Endowed with Antiproliferative Properties in Breast Cancer Cells. International journal of molecular sciences 3 39941053
2025 IL-20 Subfamily Biological Effects: Mechanistic Insights and Therapeutic Perspectives in Cancer. International journal of molecular sciences 3 40806452
2024 IL-20 is produced by CD3γδ T cells and induced in the mucosal tissues of grass carp during infection with Aeromonas hydrophila. Developmental and comparative immunology 3 38844187
2013 Potential synergy between SNP and CpG-A or IL-1β in regulating transcriptional activity of IL-20 promoter. The Journal of investigative dermatology 3 23892591

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