Affinage

IL20RB

Interleukin-20 receptor subunit beta · UniProt Q6UXL0

Length
311 aa
Mass
35.1 kDa
Annotated
2026-06-10
26 papers in source corpus 12 papers cited in narrative 12 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL20RB (IL-20R2) is a shared receptor subunit that pairs with either IL-20R1 or IL-22R1 to assemble two distinct heterodimeric receptor complexes, both of which bind IL-24 and signal through STAT transcription factors (PMID:11706020). Crystal structures of the IL-20/IL-20R1/IL-20R2 and IL-24/IL-22R1/IL-20R2 ternary complexes define how affinity-tuned cytokine–receptor interfaces allow the single shared IL-20R2 subunit to discriminate among IL-19, IL-20, and IL-24, with IL-20R2 contributing the higher-affinity contact in the type II complex (PMID:22802649, PMID:30111632); tyrosine70 of IL-20R2 is a functionally critical residue at the IL-24/IL-20R2 interface required for heterocomplex assembly and downstream JAK/STAT activation (PMID:37484532). Ligand engagement of IL-20RB activates JAK/STAT3 — and in some contexts PI3K/Akt — signaling, a circuit that places the receptor downstream of IL-23 in epidermal hyperplasia and psoriasis-like skin inflammation in mice (PMID:17074928) and that drives pro-fibrotic macrophage activation in bleomycin-induced pulmonary fibrosis (PMID:38583686). The same IL-19/IL-20RB/JAK1-STAT3 axis is co-opted in cancer, where it promotes osteoclast-driven bone metastasis of lung cancer (PMID:36006737) and stemness, chemoresistance, and metastatic seeding in pancreatic ductal adenocarcinoma (PMID:38098005, PMID:40460193); receptor expression is held in check by TAp63α-mediated promoter methylation, which is relieved when TRIM21 degrades TAp63α (PMID:40460193). Beyond its cytokine-receptor role, the Toxoplasma gondii rhoptry protein TgROP18 binds the IL-20RB extracellular domain to hijack host JAK/STAT3 signaling (PMID:32767999).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2001 High

    Established that IL-20RB is not a standalone receptor but a shared subunit of two heterodimeric complexes, resolving how a single chain serves multiple cytokines.

    Evidence Receptor binding assays in transfected COS cells with STAT activation readout in keratinocytes and BHK cells

    PMID:11706020

    Open questions at the time
    • Did not define the atomic interfaces distinguishing the two complexes
    • Did not assign ligand-specific affinities among IL-19/IL-20/IL-24
  2. 2006 High

    Placed IL-20RB downstream of IL-23 in an inflammatory cascade, defining its role in epidermal hyperplasia genetically rather than by association.

    Evidence Genetic epistasis with IL-20R2-/- knockout mice, intradermal IL-23 injection, histology

    PMID:17074928

    Open questions at the time
    • Which ligand(s) acting through IL-20RB drive the phenotype was not pinpointed
    • Downstream signaling in skin not dissected
  3. 2012 High

    Provided the atomic basis for how the shared IL-20R2 subunit discriminates cognate from noncognate ligands across type I and type II complexes.

    Evidence X-ray crystallography of the IL-20/IL-20R1/IL-20R2 ternary complex

    PMID:22802649

    Open questions at the time
    • Static structure does not capture assembly kinetics
    • Signaling-competent versus non-productive complex states not resolved
  4. 2016 Medium

    Explained discrepant knockout phenotypes by identifying an alternatively spliced IL-20RB isoform that survives exon I ablation and retains receptor function.

    Evidence Molecular cloning, PCR sequencing, imiquimod psoriasis mouse model

    PMID:27009487

    Open questions at the time
    • Relative abundance and tissue distribution of the isoform not quantified
    • Whether isoforms differ in ligand affinity not tested
  5. 2018 High

    Refined the type II complex interface, showing a missing disulfide explains IL-24 instability and that IL-20RB is the higher-affinity receptor for IL-24.

    Evidence X-ray crystallography of IL-24/IL-22R1/IL-20R2 at 2.15 Å with cell-based signaling using refolded IL-24

    PMID:30111632

    Open questions at the time
    • Affinity ranking rests partly on computational calculation
    • Single lab structure
  6. 2019 Low

    Reinforced the requirement for IL-20RB in psoriasis-like skin pathology via knockdown.

    Evidence IL-20R2 knockdown mice, imiquimod psoriasis model, histology, western blot, PCR

    PMID:31167692

    Open questions at the time
    • Partial knockdown rather than full knockout
    • No detailed pathway placement
    • Single lab
  7. 2020 Medium

    Revealed that a pathogen virulence factor can engage the IL-20RB extracellular domain to commandeer host JAK/STAT3 signaling, extending the receptor's biology beyond cognate cytokines.

    Evidence Co-IP, FRET, CRISPR double knockout, recombinant TgROP18 on cell lines with differential IL-20RB expression, phospho-STAT3 western blot

    PMID:32767999

    Open questions at the time
    • Physiological relevance during infection not established
    • Binding site on IL-20RB not mapped
    • Single lab
  8. 2022 Medium

    Defined an IL-19/IL-20RB/JAK1-STAT3 paracrine axis driving osteoclast-mediated bone metastasis, and showed therapeutic tractability via antibody blockade.

    Evidence Gain/loss-of-function in lung cancer lines, in vivo bone metastasis models, neutralizing antibody, JAK1/STAT3 phospho-western blot

    PMID:36006737

    Open questions at the time
    • Generalizability beyond bone microenvironment unclear
    • Single lab
  9. 2023 Medium

    Extended the IL-19/IL-20RB/STAT3 axis to pancreatic cancer stemness and chemoresistance, identifying STAT3 phosphorylation as the actionable node.

    Evidence Gain/loss-of-function in PDAC lines, spheroid and side-population assays, in vivo tumor and chemoresistance models, STAT3 inhibition

    PMID:38098005

    Open questions at the time
    • Contribution of other ligands not excluded
    • Single lab
  10. 2023 Medium

    Identified tyrosine70 of IL-20RB as a functionally critical interface residue using a photocaged amino acid as a reversible switch for complex assembly.

    Evidence Genetic code expansion with photocaged ortho-nitrobenzyl-tyrosine, biophysical binding and JAK/STAT signaling assays

    PMID:37484532

    Open questions at the time
    • Single residue tested in isolation
    • Single lab, single study
  11. 2025 Medium

    Established the upstream transcriptional control of IL-20RB, showing TRIM21-driven degradation of TAp63α derepresses the IL-20RB promoter to fuel PDAC progression.

    Evidence TAp63α and TRIM21 manipulation in PDAC lines, ubiquitination assays, promoter methylation analysis, JAK1-STAT3 western blot, in vivo metastasis model

    PMID:40460193

    Open questions at the time
    • Direct TAp63α occupancy at the promoter versus indirect effects not fully separated
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ligand-specific IL-20RB signaling outputs are differentially decoded across tissues (skin, lung, bone, pancreas) and whether the two complexes route to distinct downstream programs remains unresolved.
  • No unified comparison of type I versus type II signaling outputs
  • Ligand-specific transcriptional programs not mapped
  • Endogenous IL-20RB structural state in signaling-competent membranes not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0048018 receptor ligand activity 2
Localization
GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 2
Partners
IL19IL20IL20RAIL22RA1IL24TGROP18
Complex memberships
IL-20R1/IL-20R2 (type I) receptorIL-22R1/IL-20R2 (type II) receptor

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 IL-20RB (IL-20R2) is a shared subunit of two heterodimeric receptor complexes: IL-22R1/IL-20R2 and IL-20R1/IL-20R2, both of which serve as functional receptors for IL-24. COS cells transfected with either heterodimer bind IL-24 with similar saturation kinetics, and IL-24 binding to either receptor complex activates STAT transcription factors. Receptor binding assays in transfected COS cells, STAT activation assays in keratinocytes and BHK cells The Journal of biological chemistry High 11706020
2006 IL-20R2 (IL-20RB) is required for IL-23-dependent epidermal hyperplasia in mouse skin. IL-23 induces IL-19 and IL-24 expression, and whereas IL-19-/- and IL-24-/- mice still develop epidermal hyperplasia, IL-20R2-/- mice are protected, placing IL-20R2 downstream of IL-23 in this inflammatory cascade. Genetic epistasis using IL-20R2-/- knockout mice with intradermal IL-23 injection and histological readout The Journal of experimental medicine High 17074928
2012 Crystal structure of the IL-20/IL-20R1/IL-20R2 ternary complex reveals how type I (IL-20R1/IL-20R2) and type II (IL-22R1/IL-20R2) receptor complexes discriminate cognate from noncognate ligands, and how receptor-cytokine interfaces are affinity-tuned to allow distinct signaling through the shared IL-20R2 subunit by three different ligands (IL-19, IL-20, IL-24). X-ray crystallography of the IL-20/IL-20R1/IL-20R2 complex Proceedings of the National Academy of Sciences of the United States of America High 22802649
2018 Crystal structure of the IL-24/IL-22R1/IL-20R2 ternary complex at 2.15 Å resolution shows that two cysteine residues in IL-24 do not form a predicted disulfide bond (unlike related cytokines), explaining IL-24 instability; calculations indicate the IL-24–IL-20R2 interaction is slightly more stable than IL-24–IL-22R1, suggesting IL-20R2 is the higher-affinity receptor in the type II complex. X-ray crystallography of the IL-24/IL-22R1/IL-20R2 ternary complex at 2.15 Å; cell-based signaling assays with refolded IL-24 Journal of immunology High 30111632
2016 Alternative splicing of IL-20R2 (IL-20RB) produces a second isoform that survives exon I ablation, explaining why IL-20R2 exon I knockout mice do not fully recapitulate expected loss-of-function psoriatic phenotypes. The surviving isoform retains functional receptor activity. Molecular cloning of alternatively spliced transcript, PCR sequencing, imiquimod-induced psoriasis mouse model Genes and immunity Medium 27009487
2020 Toxoplasma gondii rhoptry protein TgROP18 physically interacts with the extracellular domain of IL-20RB on host cells and activates the host JAK/STAT3 pathway. STAT3 phosphorylation by recombinant TgROP18 is dose-dependent and occurs only in cells with endogenous IL-20RB expression, demonstrating that TgROP18 hijacks the IL-20RB signaling axis to activate host immune responses including TNF-α expression. Co-immunoprecipitation, FRET, CRISPR-Cas9 double knockout of TgROP16/TgROP18, recombinant protein treatment of cell lines with differential IL-20RB expression, western blot for phospho-STAT3 Parasites & vectors Medium 32767999
2022 IL-20RB mediates a direct pro-tumoral response to osteoclasts in bone metastasis of lung cancer. Tumor cells induce osteoclasts to secrete IL-19, which signals through IL-20RB on tumor cells to activate JAK1/STAT3 signaling, enhancing tumor cell proliferation in bone. Blocking IL-20RB with a neutralizing antibody suppresses bone metastasis in vivo. IL-20RB overexpression/knockdown in lung cancer cell lines, in vivo bone metastasis models, neutralizing antibody treatment, western blot for JAK1/STAT3 phosphorylation The Journal of clinical investigation Medium 36006737
2023 IL-20RB promotes stemness and chemoresistance in pancreatic cancer via STAT3 phosphorylation. IL-19 from the tumor microenvironment is the primary ligand mediating these effects. STAT3 phosphorylation inhibitors counteract IL-20RB-driven stemness and chemoresistance. IL-20RB overexpression and knockdown in pancreatic cancer cell lines, clonal/spheroid formation and side-population analysis in vitro, in vivo tumor formation and chemotherapy resistance models, pharmacological inhibition of STAT3 Journal of translational medicine Medium 38098005
2024 IL-20RB promotes pulmonary fibrosis by enhancing the activation of bone marrow-derived pro-fibrotic macrophages. Mechanistically, IL-20RB regulates Jak2/STAT3 and PI3K/Akt signaling pathways in macrophages. Absence of IL-20RB alleviates bleomycin-induced fibrosis, and neutralizing antibodies against IL-20RB reduce IPF progression in animal models. Bleomycin-induced pulmonary fibrosis mouse model, IL4/13-induced THP1 macrophage polarization, IL-20RB knockout and neutralizing antibody treatment, western blot for JAK2/STAT3 and PI3K/Akt phosphorylation Pharmacological research Medium 38583686
2023 Photocaged non-canonical amino acid (ortho-nitrobenzyl-tyrosine) introduced at tyrosine70 of IL-20R2 impairs IL-24/IL-20R2 heterocomplex assembly in the dark; UV irradiation at 365 nm decages the residue, reconstituting native tyrosine and restoring IL-24 binding and downstream JAK/STAT phosphorylation. This identifies tyrosine70 of IL-20R2 as a functionally critical residue at the IL-24/IL-20R2 interface. Genetic code expansion with photocaged non-canonical amino acids, biophysical binding assays, cell signaling assays for JAK/STAT phosphorylation Frontiers in molecular biosciences Medium 37484532
2025 The E3 ubiquitin ligase TRIM21 promotes ubiquitin-dependent degradation of TAp63α, which normally transcriptionally represses IL-20RB by inducing promoter methylation. Loss of TAp63α derepresses IL-20RB, increasing IL-20 receptor formation and activating downstream JAK1-STAT3 signaling to drive PDAC proliferation, EMT, migration, and in vivo metastatic seeding. TAp63α overexpression/knockdown in PDAC cell lines, TRIM21 manipulation, ubiquitination assays, promoter methylation analysis, JAK1-STAT3 western blot, in vivo metastasis model Science signaling Medium 40460193
2019 Knockdown of IL-20R2 (IL-20RB) in mice reduces psoriasis-like pathological changes induced by imiquimod, confirmed by reduced IL-20R2 protein and mRNA in skin tissue. IL-20R2 knockdown mice, imiquimod-induced psoriasis model, HE staining, western blot, PCR Xi bao yu fen zi mian yi xue za zhi Low 31167692

Source papers

Stage 0 corpus · 26 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis. The Journal of experimental medicine 559 17074928
2001 Interleukin 24 (MDA-7/MOB-5) signals through two heterodimeric receptors, IL-22R1/IL-20R2 and IL-20R1/IL-20R2. The Journal of biological chemistry 225 11706020
1985 Sequence of Dictyostelium DIRS-1: an apparent retrotransposon with inverted terminal repeats and an internal circle junction sequence. Cell 93 2416457
2012 Structural basis for receptor sharing and activation by interleukin-20 receptor-2 (IL-20R2) binding cytokines. Proceedings of the National Academy of Sciences of the United States of America 78 22802649
2022 IL-20RB mediates tumoral response to osteoclastic niches and promotes bone metastasis of lung cancer. The Journal of clinical investigation 76 36006737
2005 DIRS-1 and the other tyrosine recombinase retrotransposons. Cytogenetic and genome research 57 16093711
2012 ALOG domains: provenance of plant homeotic and developmental regulators from the DNA-binding domain of a novel class of DIRS1-type retroposons. Biology direct 43 23146749
1984 Dictyostelium transposable element DIRS-1 has 350-base-pair inverted terminal repeats that contain a heat shock promoter. Proceedings of the National Academy of Sciences of the United States of America 36 6326136
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
2008 Association analysis of IL20RA and IL20RB genes in psoriasis. Genes and immunity 22 18480827
2018 Crystal Structure of the Labile Complex of IL-24 with the Extracellular Domains of IL-22R1 and IL-20R2. Journal of immunology (Baltimore, Md. : 1950) 20 30111632
2024 IL20Rb aggravates pulmonary fibrosis through enhancing bone marrow derived profibrotic macrophage activation. Pharmacological research 16 38583686
1984 Transcription of Dictyostelium discoideum transposable element DIRS-1. Molecular and cellular biology 15 6096693
2019 Insertion Hot Spots of DIRS1 Retrotransposon and Chromosomal Diversifications among the Antarctic Teleosts Nototheniidae. International journal of molecular sciences 13 30736325
2020 TgROP18 targets IL20RB for host-defense-related-STAT3 activation during Toxoplasma gondii infection. Parasites & vectors 12 32767999
2013 The Dictyostelium discoideum RNA-dependent RNA polymerase RrpC silences the centromeric retrotransposon DIRS-1 post-transcriptionally and is required for the spreading of RNA silencing signals. Nucleic acids research 12 24369430
2023 IL20RB signaling enhances stemness and chemotherapy resistance in pancreatic cancer. Journal of translational medicine 11 38098005
2014 Argonaute proteins affect siRNA levels and accumulation of a novel extrachromosomal DNA from the Dictyostelium retrotransposon DIRS-1. The Journal of biological chemistry 9 25352599
2023 Regulation of IL-24/IL-20R2 complex formation using photocaged tyrosines and UV light. Frontiers in molecular biosciences 8 37484532
2025 The E3 ligase TRIM21 promotes progression of pancreatic ductal adenocarcinoma by down-regulating TAp63α and derepressing IL20RB. Science signaling 6 40460193
2022 Grass carp IL-20 binds to IL-20R2 but induces STAT3 phosphorylation via IL-20R1. Fish & shellfish immunology 6 36414129
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
2013 Detection of IL-20R1 and IL-20R2 mRNA in C57BL/6 mice astroglial cells and brain cortex following LPS stimulation. Iranian journal of immunology : IJI 4 23811545
2016 Alternative splicing directs two IL-20R2 isoforms and is responsible for the incomplete gene knockout via the exon I ablation. Genes and immunity 2 27009487
2019 [Knockdown of interleukin 20 receptor 2 (IL-20R2) inhibits the development of psoriasis induced by imiquimod in mice]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 1 31167692
2011 Purification, crystallization and preliminary X-ray diffraction analysis of the IL-20-IL-20R1-IL-20R2 complex. Acta crystallographica. Section F, Structural biology and crystallization communications 0 22232181

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