Affinage

Showing IL19 — MDA1 is a alias.

IL19

Interleukin-19 · UniProt Q9UHD0

Length
177 aa
Mass
20.5 kDa
Annotated
2026-06-10
90 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL-19 is a secreted IL-10-family cytokine that signals exclusively through the type I IL-20 receptor complex (IL-20R1/IL-20R2), driving STAT3 phosphorylation while sparing both the canonical IL-10 receptor and the type II IL-20R complex (PMID:11564763, PMID:11196675). Its expression is broadly inducible by inflammatory and microbial cues — LPS, GM-CSF, IL-4/IL-13, IL-17A, and adenosine signaling — through NF-κB and STAT6 transcriptional control, and it sustains its own production through autocrine loops while transcriptionally activating IL-10 (PMID:11196675, PMID:15827959, PMID:18539194). Functionally, IL-19 acts as a context-dependent immunomodulator: it promotes Th2 cytokine polarization in activated T cells via IL-20R1 (PMID:15557163, PMID:31114590) and serves as an upstream node in the DNA damage-induced cytokine response, where ASK1-JNK and cGAS-STING pathways induce IL-19 that is in turn required for downstream IL-1, IL-6, and IL-8 production (PMID:34932373). In the vasculature, IL-19 is broadly anti-inflammatory and atheroprotective, reducing VSMC proliferation and inflammatory gene expression by lowering cytoplasmic abundance and phosphorylation of the mRNA-stabilizing protein HuR through induction of the competing RNA-binding protein FXR1 and miR133a (PMID:20451530, PMID:30067974, PMID:29674474), inducing STAT3-dependent HO-1 to suppress ROS (PMID:22158875), and reprogramming macrophages toward an M2, PPARγ-driven phenotype that limits cholesterol uptake and lipid accumulation (PMID:26952642, PMID:28257760); genetic deletion exacerbates atherosclerosis and neointimal hyperplasia, rescued by recombinant IL-19 (PMID:24814101, PMID:29674474). IL-19 similarly suppresses hepatocyte lipogenesis via STAT3 and PPARα (PMID:34944021, PMID:41485927) and acts as a lymphangiogenic factor promoting lymphatic endothelial migration, network formation, and VE-cadherin phosphorylation (PMID:40371466). Osteocyte-derived IL-19 stimulates granulopoiesis through IL-20Rβ/STAT3 in neutrophil progenitors (PMID:33684929). In epithelial and tumor settings IL-19 is pro-inflammatory or pro-tumorigenic, amplifying IL-17A effects on keratinocytes (PMID:25046339, PMID:34616394), inducing airway MUC5AC and MMP-9 (PMID:31379870, PMID:33900049), and promoting tumor cell migration, EMT, and immunosuppression across breast cancer, glioblastoma, and Wilms tumor (PMID:22186257, PMID:40057744, PMID:40185911).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2001 High

    Established the receptor through which IL-19 signals, resolving its placement within the IL-20R rather than IL-10R system and defining STAT3 as its proximal effector.

    Evidence Receptor-binding and STAT3 phosphorylation/reporter assays in transfected cells, with comparison to IL-20 and MDA-7

    PMID:11196675 PMID:11564763

    Open questions at the time
    • Does not address tissue-specific receptor subunit usage or whether non-STAT3 effectors are engaged
    • Receptor identity tested in transfected cells, not native target cells
  2. 2005 High

    Showed how IL-19 expression is regulated and self-reinforced, identifying inducing stimuli and autocrine/IL-10 cross-regulatory loops that govern its inflammatory output.

    Evidence RT-PCR and ELISA in stimulated monocytes/PBMC; dendritic cell maturation assays; A2B adenosine receptor pharmacology; NF-κB/STAT6 siRNA, inhibitors, and ChIP at the IL-19 promoter

    PMID:11196675 PMID:15827959 PMID:16778150 PMID:18539194

    Open questions at the time
    • Promoter dissection focused on airway epithelium; cell-type generality of NF-κB/STAT6 control not established
    • Functional consequence of autocrine IL-19/IL-10 balance in vivo not defined
  3. 2004 Medium

    Defined IL-19 as a driver of Th2 polarization, framing it as an immunomodulatory rather than purely effector cytokine.

    Evidence Recombinant IL-19 stimulation of resting vs activated T cells with ELISA cytokine readouts

    PMID:15557163

    Open questions at the time
    • Mechanism linking IL-20R/STAT3 to Th2 transcriptional program not resolved
    • Activation-dependence mechanism not defined
  4. 2010 High

    Identified the post-transcriptional axis underlying IL-19's anti-inflammatory action in vasculature: suppression of HuR-mediated mRNA stabilization.

    Evidence Phospho-HuR and PKCα activity assays, actinomycin D mRNA stability assays, and HuR siRNA phenocopy in VSMCs

    PMID:20451530

    Open questions at the time
    • Link from IL-20R/STAT3 signaling to PKCα inactivation not mechanistically connected
    • Single cell type (VSMC)
  5. 2011 High

    Connected IL-19/STAT3 signaling to an antioxidant program, showing direct STAT3-dependent transcriptional induction of HO-1 that lowers ROS.

    Evidence HO-1 promoter STAT-site mutation, STAT3 and HO-1 siRNA, and ROS functional rescue in VSMCs

    PMID:22158875

    Open questions at the time
    • Cell-type selectivity (no HO-1 induction in endothelium) mechanism unexplained
    • In vivo relevance of HO-1 arm not tested in this study
  6. 2014 High

    Provided genetic proof that endogenous IL-19 restrains vascular injury responses, moving the cytokine from a pharmacological agent to a physiological regulator.

    Evidence Carotid ligation in IL-19 KO mice with recombinant IL-19 rescue; KO VSMC proliferation/migration and inflammatory marker assays

    PMID:24814101

    Open questions at the time
    • Cell-autonomous vs systemic contributions not fully separated
    • Receptor/signaling pathway not dissected in this model
  7. 2016 High

    Demonstrated IL-19 controls macrophage polarization and lipid handling, extending its atheroprotection to a metabolic-reprogramming mechanism.

    Evidence Recombinant IL-19 in LDLR-/- atherosclerosis model; STAT3/STAT6/KLF4/PPARγ immunoblotting; cholesterol uptake/efflux assays

    PMID:26952642

    Open questions at the time
    • Relative contribution of each transcription factor not ranked
    • Whether macrophage effects require IL-20R1 not directly tested
  8. 2018 High

    Resolved the molecular basis of IL-19-mediated HuR suppression by identifying FXR1 and miR133a as the effectors that destabilize inflammatory mRNAs, and confirmed genetic atheroprotection.

    Evidence LC-MS/MS, RNA-dependent Co-IP, RNA EMSA, RIP, siRNA/overexpression in VSMCs; miR133a/LDLRAP1 validation; Il19/Ldlr double-KO atherosclerosis with bone marrow transplantation

    PMID:28257760 PMID:29674474 PMID:30067974

    Open questions at the time
    • How IL-19 signaling induces FXR1 and miR133a transcription not defined
    • Interplay between FXR1, miR133a, and HuR not quantitatively integrated
  9. 2019 High

    Established receptor dependence of IL-19's Th2/allergic actions and revealed pro-pathogenic epithelial functions in airway disease.

    Evidence IL-20R1 KO mice and anti-IL-19/anti-IL-20R1 antibodies in allergen-challenge asthma models; STAT3 inhibitor and IL-20R2 siRNA in nasal epithelium for MUC5AC; IL-20R1 siRNA for MMP-9

    PMID:31114590 PMID:31379870 PMID:33900049

    Open questions at the time
    • Why IL-19 is anti-inflammatory in vasculature but pro-inflammatory in airway not mechanistically explained
    • Downstream effectors of epithelial STAT3/ERK/NF-κB outputs not fully mapped
  10. 2021 High

    Placed IL-19 as an upstream node of the DNA damage-induced secretory cytokine cascade, distinct from PDL1 induction.

    Evidence siRNA epistasis with ASK1-JNK and cGAS-STING pathway inhibitors across multiple DNA-damaging stimuli; downstream IL-1/IL-6/IL-8 measurement

    PMID:34932373

    Open questions at the time
    • Identity of IL-19 target cells driving downstream cytokines not defined
    • Whether the DNA-damage IL-19 signal uses IL-20R/STAT3 autocrine signaling not tested
  11. 2021 High

    Identified a hematopoietic niche function: osteocyte-derived IL-19 drives granulopoiesis via IL-20Rβ/STAT3 in neutrophil progenitors, with translational neutropenia-reversal potential.

    Evidence Dmp1-Cre mTORC1 gain/loss models, IL-19 neutralization, IL-20Rβ depletion, and recombinant IL-19 rescue of neutropenia

    PMID:33684929

    Open questions at the time
    • Direct progenitor-intrinsic vs niche-mediated effects not fully separated
    • Comparison of IL-20Rβ vs full type I receptor usage in progenitors not resolved
  12. 2021 Medium

    Extended IL-19's lipid-suppressive role to hepatocytes, defining a Kupffer-cell-to-hepatocyte STAT3/PPARα axis that protects against NAFLD/NASH.

    Evidence IL-19 KO CDAHFD NASH model; palmitate-treated HepG2 lipid, ATP, and PPARα assays

    PMID:34944021 PMID:41485927

    Open questions at the time
    • Cell-type-specific receptor requirement on hepatocytes not genetically tested
    • Mechanistic link from STAT3 to PPARα activity not resolved
  13. 2025 High

    Defined IL-19 as a lymphangiogenic factor regulating lymphatic endothelial junctions and drainage, broadening its vascular role beyond arterial protection.

    Evidence HDLEC migration/network/permeability assays with VE-cadherin phosphorylation; Il19/Ldlr dKO lymphatic drainage and junction analysis

    PMID:40371466

    Open questions at the time
    • Signaling pathway from IL-20R to VE-cadherin phosphorylation not dissected
    • Whether lymphatic effects contribute to atheroprotection not directly linked
  14. 2025 Medium

    Documented context-dependent pro-tumorigenic and tissue-remodeling roles, showing IL-19 promotes EMT, tumor migration, immunosuppression, and fibrosis modulation across diverse tissues.

    Evidence CRISPR KO and pathway analyses across breast cancer, glioblastoma (IL-19/WISP1, TAM reprogramming), Wilms tumor (STAT3/SNAIL EMT), keratinocyte psoriasis models, osteoarthritis (Hippo/YAP1), and fibroblast TGF-β/ERK/p38 signaling

    PMID:22186257 PMID:23582717 PMID:25046339 PMID:31539104 PMID:34616394 PMID:40057744 PMID:40185911 PMID:40647365 PMID:41103413 PMID:42155391

    Open questions at the time
    • Unified explanation for opposing pro- vs anti-inflammatory outcomes across tissues lacking
    • Many tumor mechanisms rest on single-lab CRISPR/pathway readouts without receptor-level dissection

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single IL-20R1/IL-20R2-STAT3 signaling input produces opposing anti-inflammatory/atheroprotective versus pro-inflammatory/pro-tumorigenic outcomes in different target cells.
  • No mechanism distinguishing protective vs pathogenic signaling branches
  • Cell-type-specific co-factors and receptor-subunit usage not systematically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-8953897 Cellular responses to stimuli 1
Partners
IL20RAIL20RB

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 IL-19 binds to and signals exclusively through the type I IL-20R complex (IL-20Rα/IL-20Rβ; also called CRF2-8/IL-20R1 and DIRS1/IL-20R2), resulting in STAT3 phosphorylation and activation of STAT-binding promoter elements. Unlike IL-20 and MDA-7, IL-19 does not bind the type II IL-20R complex (IL-22R/IL-20Rβ). Receptor-binding assays and STAT3 phosphorylation/reporter gene assays in transfected cells Journal of immunology High 11564763
2000 IL-19 does not bind or signal through the canonical IL-10 receptor complex, indicating a distinct, as-yet-unidentified receptor at the time of initial cloning. IL-19 mRNA is induced in monocytes by LPS, and expression is potentiated by IL-4 or IL-13 in LPS-stimulated monocytes; GM-CSF can directly induce IL-19 gene expression in monocytes. Receptor-binding assay (negative result for IL-10R); RT-PCR for expression in LPS-, IL-4-, IL-13-, and GM-CSF-stimulated monocytes Genes and immunity Medium 11196675
2002 Mouse IL-19 treatment of monocytes induces IL-6 and TNF-α production and triggers monocyte apoptosis and reactive oxygen species production. IL-19-induced apoptosis is mediated through TNF-α. ELISA for cytokine production; apoptosis assays in cultured mouse monocytes treated with recombinant IL-19 Journal of immunology Medium 12370360
2004 IL-19 induces IL-4, IL-5, IL-10, and IL-13 production by activated (but not resting) T cells, promoting Th2 cytokine polarization. Activation of T cells is required for IL-19-induced IL-13 production. In vitro cytokine stimulation of purified T cells with recombinant IL-19; ELISA for cytokine measurement Journal of immunology Medium 15557163
2005 IL-19 induces its own expression in an autocrine/auto-induction loop in PBMC; it also transcriptionally activates IL-10 expression (dose-dependent, detected at mRNA and protein level). IL-10 in turn potently downregulates this IL-19 auto-induction. IL-19 stimulation of dendritic cell maturation increases intracellular IL-10 without affecting IL-12. ELISA for IL-10 secretion; quantitative RT-PCR for mRNA; dendritic cell maturation assay European journal of immunology Medium 15827959
2006 IL-19 increases IL-19 expression in airway epithelial cells via A2B adenosine receptor activation: NECA (adenosine analog) increases IL-19 release from human bronchial epithelial cells (HBECs) via A2B receptors (blocked by selective A2B antagonist CVT-6694). Released IL-19 activates THP-1 monocytic cells to increase TNF-α release, and TNF-α in turn upregulates A2B receptor expression in HBECs, forming a positive feedback loop. ELISA for IL-19 and TNF-α; pharmacological blockade with selective A2B antagonist; THP-1 activation assay American journal of respiratory cell and molecular biology Medium 16778150
2008 IL-19 transcriptional regulation in airway epithelium is mediated by NF-κB and STAT6. IL-17A induces IL-19 via NF-κB; co-treatment with IL-13 shifts regulation to STAT6-dependent transcription. STAT6-binding elements in the IL-19 promoter were confirmed by chromatin immunoprecipitation. siRNA knockdown of NF-κB and STAT6; chemical inhibitors; chromatin immunoprecipitation (ChIP) for STAT6 at IL-19 promoter; reporter assays Journal of allergy and clinical immunology High 18539194
2008 IL-19 activates STAT3 in rheumatoid synovial cells (RASCs) and increases IL-6 production; IL-19 also reduces serum-starvation-induced RASC apoptosis, suggesting autocrine pro-survival signaling via IL-20R1/IL-20R2 in synovial cells. Western blot for STAT3 phosphorylation; ELISA for IL-6; Hoechst staining, annexin V flow cytometry, and caspase-3 activity for apoptosis Rheumatology Medium 18397956
2010 IL-19 reduces VSMC proliferation and inflammatory gene expression (Cyclin D1, IL-1β, IL-8, COX2) by reducing cytoplasmic abundance of the mRNA stability factor HuR. Mechanistically, IL-19 reduces serine phosphorylation of HuR and reduces activation of PKCα, a known regulator of HuR cytoplasmic translocation. Actinomycin D experiments confirmed IL-19 reduces mRNA stability of proliferative/inflammatory transcripts; siRNA knockdown of HuR phenocopies this effect. Western blot for HuR and phospho-HuR; PKCα activity assay; actinomycin D mRNA stability assay; siRNA knockdown of HuR; RT-PCR/immunoblot for target gene expression Journal of molecular and cellular cardiology High 20451530
2011 IL-19 induces heme oxygenase-1 (HO-1) mRNA and protein in vascular smooth muscle cells (VSMCs) via STAT3 activation. IL-19-induced HO-1 expression is abolished by STAT3 siRNA or mutation of the consensus STAT binding site in the HO-1 promoter. HO-1 mediates the IL-19-driven decrease in reactive oxygen species (ROS), as HO-1 siRNA attenuates this effect. IL-19 does not induce HO-1 in endothelial cells. RT-PCR, immunoblot, ELISA for HO-1; STAT3 siRNA; HO-1 promoter mutation assay; HO-1 siRNA; ROS assay; Annexin V flow cytometry for apoptosis Journal of Biological Chemistry High 22158875
2013 IL-19 promotes skin wound healing by inducing keratinocyte growth factor (KGF) expression in fibroblasts; IL-19-stimulated fibroblast conditioned medium promotes keratinocyte proliferation. IL-19 increases keratinocyte migration but not direct proliferation; KGF (not IL-19) directly drives keratinocyte proliferation. Real-time PCR for IL-19 and KGF; BrdU proliferation assay; transwell migration assay; in vivo wound-healing model in BALB/C mice with topical IL-19 Cytokine Medium 23582717
2014 In psoriasis, IL-19 is induced in keratinocytes by IL-17A, and this induction is amplified by TNF-α and IL-22. IL-19 amplifies many IL-17A effects on keratinocytes, including upregulation of β-defensins, IL-19 itself, IL-23p19, and Th17/neutrophil-attracting chemokines. IL-19 increases S100A7/8/9 and modestly IL-1β, IL-20, CXCL8, and MMP1. IL-19 alone does not affect keratinocyte differentiation, proliferation, or migration. Cytokine stimulation of keratinocytes; RT-PCR and ELISA for multiple targets; keratinocyte functional assays (differentiation, proliferation, migration) Journal of investigative dermatology Medium 25046339
2014 IL-19 reduces ligation-induced neointimal hyperplasia in vivo: IL-19 knockout (KO) mice show significantly higher neointima/intima ratio after carotid artery ligation, which is rescued by recombinant IL-19 injection. VSMCs from KO mice proliferate and migrate more rapidly than wild-type, reversible by IL-19 addition. KO VSMCs express greater inflammatory mRNA (IL-1β, TNF-α, MCP-1) and greater adhesion molecule expression, with enhanced monocyte adhesion. Carotid ligation in IL-19 KO vs WT mice; morphometric analysis; VSMC proliferation and migration assays; RT-PCR and ELISA for inflammatory mediators; monocyte adhesion assay American journal of pathology High 24814101
2016 Exogenous IL-19 halts progression of preformed atherosclerotic plaque in LDLR-/- mice and promotes M2 macrophage polarization. IL-19 activates STAT3, STAT6, KLF4, and PPARγ pathways in macrophages leading to M2 polarization. IL-19 regulates macrophage lipid metabolism via PPARγ-dependent modulation of scavenger receptor-mediated cholesterol uptake and ABCA1-mediated cholesterol efflux. In vivo atherosclerosis model in LDLR-/- mice with recombinant IL-19; plaque morphometry; immunostaining for macrophage phenotype markers; Western blot for STAT3/STAT6/KLF4/PPARγ; cholesterol uptake and efflux assays American journal of pathology High 26952642
2017 IL-19 induces expression of miR133a in VSMCs, which targets and reduces mRNA abundance, stability, and protein expression of LDLRAP1 (LDL receptor adaptor protein 1). This reduces oxLDL uptake by VSMCs. IL-19 reduces lipid accumulation in VSMCs through this miR133a/LDLRAP1 mechanism. qRT-PCR and immunoblot for miR133a and LDLRAP1; mRNA stability assay; siRNA knockdown of LDLRAP1; miR133a transfection; oxLDL uptake assay; lipid accumulation assay Journal of molecular and cellular cardiology High 28257760
2018 FXR1 is identified as an IL-19-responsive RNA-binding protein in VSMCs that destabilizes pro-inflammatory mRNAs. FXR1 was identified as an HuR-interacting protein by LC-MS/MS; their association is RNA-dependent (abrogated by RNase treatment). FXR1 overexpression reduces abundance and stability of inflammatory mRNAs; FXR1 siRNA increases them. FXR1 binds AU-rich elements and a 3' UTR element of TNFα mRNA (RNA EMSA and RIP). FXR1 expression is induced by IL-19, and FXR1 is required for IL-19-mediated reduction of HuR. LC-MS/MS proteomics; Co-IP with RNase treatment; siRNA knockdown and overexpression; mRNA stability assays; RNA EMSA; RNA immunoprecipitation (RIP); Western blot Cell reports High 30067974
2018 Genetic deletion of IL-19 (Il19-/- × Ldlr-/- double KO mice) exacerbates atherosclerosis with increased plaque burden, Th1/M1 polarization, and TNF-α expression compared to Ldlr-/- controls. dKO mice have increased HuR abundance in spleen, aortic arch, and bone marrow-derived cells. IL-19 induces miR133a, which reduces HuR abundance; miR133a levels are lower in dKO mice. Bone marrow transplantation suggests immune cells participate in IL-19 protection. Double-KO mouse model; high-fat diet atherosclerosis; qRT-PCR and Western blot for HuR and cytokines; miR133a measurement; bone marrow transplantation Arteriosclerosis, thrombosis, and vascular biology High 29674474
2019 IL-19 signaling through IL-20R1 is required for IL-19-induced Th2 cell differentiation; IL-20R1-deficient mice have abolished IL-19-induced Th2 responses. Blocking IL-19 or IL-20R1 with antibodies ameliorates allergen (Der p)-induced airway hyperresponsiveness, immune cell infiltration, and Th2 cytokine expression in rodent asthma models. IL-20R1 KO mouse model; anti-IL-20R1 mAb and anti-IL-19 antibodies; allergen challenge (house dust mite and ovalbumin); measurement of AHR, BAL cellularity, cytokines; in vitro Th2 differentiation assay Frontiers in immunology High 31114590
2019 IL-19 upregulates MUC5AC production in primary human nasal epithelial cells via the STAT3 signaling pathway. STAT3 inhibitor (cryptotanshinone) and IL-20R2 siRNA knockdown both attenuate IL-19-induced MUC5AC expression. RT-qPCR, ELISA, Western blot, confocal microscopy for MUC5AC; STAT3 inhibitor (cryptotanshinone); IL-20R2 siRNA knockdown Frontiers in immunology Medium 31379870
2019 IL-19 promotes breast cancer cell migration by inducing fibronectin expression and assembly; IL-19 also induces IL-1β, IL-6, TGF-β, MMP2, MMP9, and CXCR4 transcripts in 4T1 breast cancer cells. Anti-IL-19 mAb inhibits fibronectin expression and cell migration. Hypoxia induces IL-19 and CXCR4 expression, which is blocked by anti-IL-19 mAb. IL-19 overexpression in noninvasive 67NR cells increases proliferation and migration; in vivo, IL-19-overexpressing 67NR clones form larger tumors with more lung metastatic micronodules. RT-PCR and immunoblot for target genes; proliferation and migration assays; anti-IL-19 mAb blockade; IL-19 knockdown cells; subcutaneous tumor implantation in mice; lung metastasis quantification Clinical cancer research Medium 22186257
2021 IL-19 expression is induced by DNA damage through two distinct pathways: the ASK1-JNK pathway (critical for ionizing radiation response) and the cGAS-STING pathway (responsive to both ionizing radiation and ATR inhibition). IL-19 expression is upstream and required for subsequent induction of IL-1, IL-6, and IL-8 following DNA damage; suppression of IL-19 substantially reduces these cytokines. The cGAS-STING-dependent induction of PDL1 after DNA damage is independent of IL-19. siRNA suppression of IL19; pathway inhibitors; diverse DNA-damaging stimuli; cytokine measurement; genetic pathway epistasis Science signaling High 34932373
2021 Osteocyte-derived IL-19 stimulates granulopoiesis by activating IL-20Rβ/STAT3 signaling in neutrophil progenitors. Constitutive mTORC1 activation in osteocytes (Dmp1-Cre mice) increases IL-19 production and promyelocyte/myelocyte expansion; mTORC1 inactivation reduces IL-19 and neutrophil numbers. Neutralizing endogenous IL-19 or depleting IL-20Rβ inhibits neutrophil development. Exogenous IL-19 reverses chemotherapy/irradiation/chloramphenicol-induced neutropenia more efficiently than G-CSF. Dmp1-Cre conditional mTORC1 activation/inactivation mouse models; IL-19 neutralization; IL-20Rβ depletion; bone marrow analysis; neutropenia models with recombinant IL-19 rescue Blood High 33684929
2021 IL-19 promotes keratinocyte migration but inhibits keratinocyte apoptosis via the Bcl-2/Caspase-3 signaling axis. IL-19 knockdown in M5-stimulated HaCaT cells increases apoptosis, reduces Bcl-2, and increases cleaved caspase-3/PARP; IL-19 overexpression reverses these effects. In vivo, IL-19 knockdown in an imiquimod-induced psoriasis-like mouse model reduces epidermal hyperplasia and enhances keratinocyte apoptosis while modulating Bcl-2/caspase-3. CCK-8 assay; flow cytometry; TUNEL; qPCR; Western blot for Bcl-2/caspase-3/PARP; siRNA knockdown and overexpression in HaCaT cells; imiquimod mouse model International immunopharmacology Medium 42155391
2021 IL-17A directly induces IL-19 and IL-24 expression in skin fibroblasts and keratinocytes. Psoriatic skin fibroblasts intrinsically express higher levels of IL-19 than healthy fibroblasts. IL-17A neutralization in fibroblast-T cell co-culture suppresses IL-19 and IL-24. IL-19 and IL-24 upregulation (but not IL-17A) coincides with increased keratinocyte proliferation in the imiquimod psoriasis mouse model. Primary skin fibroblast culture (psoriatic vs. healthy); T cell co-culture; anti-IL-17A neutralization; imiquimod mouse model with anti-IL-10 to amplify IL-17A; histology, flow cytometry; RT-PCR Frontiers in immunology Medium 34616394
2021 IL-19 deficiency in a NAFLD/NASH mouse model (CDAHFD diet) results in significantly worse liver injury, inflammation, and fibrosis, with higher IL-6, TNF-α, and TGF-β. In vitro, IL-19 decreases palmitate-induced triglyceride and cholesterol accumulation in HepG2 cells, reduces fatty acid synthesis-related enzyme expression, and increases ATP content, indicating IL-19 suppresses lipid metabolism in hepatocytes. IL-19 KO mouse NAFLD/NASH model; liver histology; qRT-PCR and ELISA for cytokines; in vitro palmitate treatment of HepG2 cells with IL-19; lipid content assay; ATP measurement Cells Medium 34944021
2021 In the liver, IL-19 is primarily produced by Kupffer cells and acts on hepatocytes to activate STAT3 signaling, suppress lipogenic gene expression, enhance ATP production, and increase PPARα activity, thereby shifting fatty acid utilization toward energy metabolism and attenuating lipid accumulation. NAFLD/NASH mouse model; cell-type-specific analysis; STAT3 signaling assay; lipogenic gene expression; ATP and PPARα activity measurements Nihon yakurigaku zasshi. Folia pharmacologica Japonica Medium 41485927
2021 IL-19 in glioblastoma promotes TMZ-resistant GBM cell migration and invasion through a novel IL-19/WISP1 signaling pathway. IL-19 blockade reprograms tumor-associated macrophages toward weakened pro-tumoral phenotypes with reduced Arginase 1 expression. Il19-/- M2-like BMDM with lower Arginase 1 lose the ability to suppress CD8 T cell activation. CRISPR Il-19-/- cell lines and mice; single-cell RNA sequencing; cytokine array; BMDM activation assays; CD8 T cell co-culture; in vivo GBM models Journal of biomedical science Medium 40057744
2021 IL-19 contributes to the pathogenesis of inflammatory bowel disease: IL-19 expression in macrophages is induced by microbial (TLR ligand) stimulation; IL-19-deficient mice have attenuated DSS colitis with reduced numbers of IL-6-producing macrophages in the inflamed colonic lamina propria. IL-19 KO mouse DSS colitis model; flow cytometry for IL-6-producing macrophages; TLR ligand stimulation of macrophages; gene expression in patient biopsies Journal of immunology Medium 28864472
2019 IL-19 inhibits TGF-β signaling in fibroblasts via ERK and p38 MAPK pathways: IL-19 downregulates TGF-β receptor expression and inhibits phosphorylated ERK and p38 in a concentration-dependent manner. In vivo, IL-19 reduces TGF-β and CTGF expression and suppresses extracellular matrix formation (α-SMA, collagen-1, fibronectin) in spinal scar tissues. Western blot for TGF-β receptor, p-ERK, p-p38; in vitro fibroblast pretreatment; rat laminectomy model with intravenous IL-19; qRT-PCR and Western blot for fibrosis markers in vivo European review for medical and pharmacological sciences Medium 31539104
2021 IL-19 upregulates MMP-9 production in human nasal epithelial cells via the ERK and NF-κB signaling pathways. ERK inhibitor and NF-κB inhibitor each attenuate IL-19-induced MMP-9 production. siRNA knockdown of IL-20R1 suppresses ERK and NF-κB pathway activation and decreases MMP-9 expression. IL-13 and IL-17A stimulate IL-19 production in nasal epithelial cells. RT-qPCR, ELISA, Western blot, immunofluorescence for MMP-9; ERK and NF-κB pathway inhibitors; IL-20R1 siRNA knockdown; cytokine stimulation of HNECs Clinical and translational allergy Medium 33900049
2025 IL-19 is a lymphangiogenic factor: it induces migration, network formation, and proliferation of human dermal lymphatic endothelial cells (HDLECs); induces rapid VE-cadherin phosphorylation and increases HDLEC monolayer permeability; mitigates oxLDL-associated decrease in HDLEC permeability. In vivo, Il19/Ldlr double KO mice on high-fat diet have impaired lymphatic drainage, decreased lymphatic branch points, and increased percentage of zippered junctions compared with Ldlr-/- controls. Cultured HDLEC migration and network formation assays; immunocytochemistry for VE-cadherin; electric cell-substrate impedance sensing for permeability; RNA sequencing; Il19/Ldlr dKO mouse model; in vivo lymphatic drainage assay; lymphatic vessel visualization Arteriosclerosis, thrombosis, and vascular biology High 40371466
2025 TOPK kinase (activated by solar UV) drives IL-19 expression in cutaneous squamous cell carcinoma and fibroblasts. TOPK knockdown reduces IL-19 expression and secretion. IL-19 in turn activates PI3K/AKT, ERK, and TOPK pathways in cSCC cells, creating a positive feedback loop. Chronic TGF-β exposure increases IL-19 expression and activates fibroblasts. IL-19 promotes cSCC growth. RNA-seq on TOPK KO vs. WT mice with/without UV; Western blotting; immunofluorescence; luciferase assays; 3D spheroid and Transwell co-culture; TOPK knockdown Cancers Medium 40647365
2025 IL-19 promotes GBM cell migration via a novel IL-19/WISP1 signaling pathway, and IL-19 suppresses Hippo signaling via modulation of YAP1 phosphorylation in osteoarthritis (OA). IL-19 in OA joints is primarily derived from synovial M2 macrophages. IL-19 mitigates IL-1β-induced OA in a chondrocyte model and in an ACLT-induced OA mouse model by inhibiting the Hippo pathway and YAP1 phosphorylation. IL-1β-induced chondrocyte inflammation model; ACLT-induced OA mouse model; Western blot and immunostaining for YAP1 phosphorylation and Hippo pathway components; cell-type-specific IL-19 source identification Frontiers in immunology Medium 41103413
2025 IL-19 and IL-20RA promote epithelial-mesenchymal transition (EMT) in Wilms tumor through the STAT3/SNAIL pathway, contributing to tumor progression. CRISPR experiments; STAT3/SNAIL pathway analysis; in vitro and in vivo tumor progression assays; CNV and methylation analysis Scientific reports Medium 40185911

Source papers

Stage 0 corpus · 90 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
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
2002 IL-19 induces production of IL-6 and TNF-alpha and results in cell apoptosis through TNF-alpha. Journal of immunology (Baltimore, Md. : 1950) 249 12370360
2000 Cloning, expression and initial characterization of interleukin-19 (IL-19), a novel homologue of human interleukin-10 (IL-10). Genes and immunity 237 11196675
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 IL-19 induced Th2 cytokines and was up-regulated in asthma patients. Journal of immunology (Baltimore, Md. : 1950) 149 15557163
2014 IL-19 is a component of the pathogenetic IL-23/IL-17 cascade in psoriasis. The Journal of investigative dermatology 142 25046339
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
2007 IL-19 and IL-20: two novel cytokines with importance in inflammatory diseases. Expert opinion on therapeutic targets 99 17465720
2006 A2B adenosine receptors induce IL-19 from bronchial epithelial cells, resulting in TNF-alpha increase. American journal of respiratory cell and molecular biology 92 16778150
2008 Potentiation of IL-19 expression in airway epithelia by IL-17A and IL-4/IL-13: important implications in asthma. The Journal of allergy and clinical immunology 89 18539194
2005 Human IL-19 regulates immunity through auto-induction of IL-19 and production of IL-10. European journal of immunology 77 15827959
2003 IL-10 subfamily members: IL-19, IL-20, IL-22, IL-24 and IL-26. Immunology letters 72 12941475
2014 Expression of interleukin (IL)-19 and IL-24 in inflammatory bowel disease patients: a cross-sectional study. Clinical and experimental immunology 68 24527982
2008 Expression of IL-19 and its receptors in RA: potential role for synovial hyperplasia formation. Rheumatology (Oxford, England) 67 18397956
2010 Expression of IL-10 family cytokines in rheumatoid arthritis: elevated levels of IL-19 in the joints. Scandinavian journal of rheumatology 62 20001767
2017 Over-expression of mutated ZmDA1 or ZmDAR1 gene improves maize kernel yield by enhancing starch synthesis. Plant biotechnology journal 58 28557341
2011 Upregulated IL-19 in breast cancer promotes tumor progression and affects clinical outcome. Clinical cancer research : an official journal of the American Association for Cancer Research 58 22186257
2007 Association analysis of IL19, IL20 and IL24 genes in palmoplantar pustulosis. The British journal of dermatology 55 17263806
2010 Il-19 reduces VSMC activation by regulation of mRNA regulatory factor HuR and reduction of mRNA stability. Journal of molecular and cellular cardiology 53 20451530
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
2010 IL-19, IL-20 and IL-24: potential therapeutic targets for autoimmune diseases. Expert opinion on therapeutic targets 50 21073280
2011 Interleukin-19 (IL-19) induces heme oxygenase-1 (HO-1) expression and decreases reactive oxygen species in human vascular smooth muscle cells. The Journal of biological chemistry 45 22158875
2009 Psychological stress increases expression of IL-10 and its homolog IL-19 via beta-adrenoceptor activation: reversal by the anxiolytic chlordiazepoxide. Brain, behavior, and immunity 45 19159673
2008 IL-19 is involved in the pathogenesis of endotoxic shock. Shock (Augusta, Ga.) 43 18246602
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
2021 Interleukin-17A Drives IL-19 and IL-24 Expression in Skin Stromal Cells Regulating Keratinocyte Proliferation. Frontiers in immunology 38 34616394
2016 IL-19 Halts Progression of Atherosclerotic Plaque, Polarizes, and Increases Cholesterol Uptake and Efflux in Macrophages. The American journal of pathology 38 26952642
2011 IL-19 as a potential therapeutic in autoimmune and inflammatory diseases. Current pharmaceutical design 38 22103848
2014 Astrocytes produce IL-19 in response to bacterial challenge and are sensitive to the immunosuppressive effects of this IL-10 family member. Glia 36 24677051
2013 Interleukin (IL)-19 promoted skin wound healing by increasing fibroblast keratinocyte growth factor expression. Cytokine 36 23582717
2018 FXR1 Is an IL-19-Responsive RNA-Binding Protein that Destabilizes Pro-inflammatory Transcripts in Vascular Smooth Muscle Cells. Cell reports 34 30067974
2018 Genetic Deletion of IL-19 (Interleukin-19) Exacerbates Atherogenesis in Il19-/-×Ldlr-/- Double Knockout Mice by Dysregulation of mRNA Stability Protein HuR (Human Antigen R). Arteriosclerosis, thrombosis, and vascular biology 33 29674474
2012 Increased expression of IL-19 in the epithelium of patients with chronic rhinosinusitis and nasal polyps. Allergy 32 22583192
2017 Induction of MiR133a expression by IL-19 targets LDLRAP1 and reduces oxLDL uptake in VSMC. Journal of molecular and cellular cardiology 31 28257760
2007 Expression of IL-19 correlates with Th2 cytokines in uraemic patients. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 31 17449492
2017 The Stimulation of Macrophages with TLR Ligands Supports Increased IL-19 Expression in Inflammatory Bowel Disease Patients and in Colitis Models. Journal of immunology (Baltimore, Md. : 1950) 30 28864472
2014 IL-19 reduces ligation-mediated neointimal hyperplasia by reducing vascular smooth muscle cell activation. The American journal of pathology 30 24814101
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
2021 Osteocytes regulate neutrophil development through IL-19: a potent cytokine for neutropenia treatment. Blood 29 33684929
2007 WD40 protein Mda1 is purified with Dnm1 and forms a dividing ring for mitochondria before Dnm1 in Cyanidioschyzon merolae. Proceedings of the National Academy of Sciences of the United States of America 27 17360593
2002 VEGF(121), VEGF(165) overexpression enhances tumorigenicity in U251 MG but not in NG-1 glioma cells. Cancer research 26 11912165
2019 Exogenous IL-19 attenuates acute ischaemic injury and improves survival in male mice with myocardial infarction. British journal of pharmacology 25 30460984
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
1998 Cross-talking among Drosophila nuclear receptors at the promiscuous response element of the ng-1 and ng-2 intermolt genes. Journal of molecular biology 23 9466931
2018 The roles of IL-19 and IL-20 in the inflammation of degenerative lumbar spondylolisthesis. Journal of inflammation (London, England) 22 30250404
2019 Increased TSLP, IL-33, IL-25, IL-19, IL 21 and amphiregulin (AREG) levels in chronic rhinosinusitis with nasal polyp. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery 21 30888496
2019 Blocking IL-19 Signaling Ameliorates Allergen-Induced Airway Inflammation. Frontiers in immunology 21 31114590
2020 Characterization of IL-19, -20, and -24 in acute and chronic kidney diseases reveals a pro-fibrotic role of IL-24. Journal of translational medicine 20 32306980
2021 The role and transformative potential of IL-19 in atherosclerosis. Cytokine & growth factor reviews 19 34600839
2019 IL-19 Up-Regulates Mucin 5AC Production in Patients With Chronic Rhinosinusitis via STAT3 Pathway. Frontiers in immunology 19 31379870
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
2021 IL-19 Contributes to the Development of Nonalcoholic Steatohepatitis by Altering Lipid Metabolism. Cells 18 34944021
2019 Expression of interleukin (IL)-10 family cytokines in aqueous humour of patients with specific endogenous uveitic entities: elevated levels of IL-19 in human leucocyte antigen-B27-associated uveitis. Acta ophthalmologica 18 30761764
2021 IL-19 induced by IL-13/IL-17A in the nasal epithelium of patients with chronic rhinosinusitis upregulates MMP-9 expression via ERK/NF-κB signaling pathway. Clinical and translational allergy 15 33900049
2018 Treatment with IL-19 improves locomotor functional recovery after contusion trauma to the spinal cord. British journal of pharmacology 15 29500933
2025 IL-19 as a promising theranostic target to reprogram the glioblastoma immunosuppressive microenvironment. Journal of biomedical science 14 40057744
2010 Association analysis of genes of the IL19 cluster and their receptors in vitiligo patients. Dermatology (Basel, Switzerland) 14 20699607
2014 Interleukins (ILs), a fascinating family of cytokines. Part I: ILs from IL-1 to IL-19. Theoretical biology forum 13 25936211
2021 Induction of IL19 expression through JNK and cGAS-STING modulates DNA damage-induced cytokine production. Science signaling 11 34932373
2019 Exogenous IL-19 mediates downregulation of TGF-β through Erk and p38 pathway to inhibit epidural fibrosis. European review for medical and pharmacological sciences 11 31539104
2019 CD4 recovery is associated with genetic variation in IFNγ and IL19 genes. Antiviral research 10 31386862
2022 Elevated IL-19 Serum Levels in Patients With Pernicious Anemia and Autoimmune Gastritis. Frontiers in immunology 9 35479078
2015 Cloning of interleukin-10 from African clawed frog (Xenopus tropicalis), with the Finding of IL-19/20 homologue in the IL-10 locus. Journal of immunology research 9 25759841
2022 Comparison of TNF-α and IL-19 concentrations at different stages of breast cancer. Journal of medicine and life 7 35928364
2021 IL-10 and Its Related Superfamily Members IL-19 and IL-24 Provide Parallel/Redundant Immune-Modulation in Loa loa Infection. The Journal of infectious diseases 7 32561912
2021 Combination of FLG mutations and SNPs of IL-17A and IL-19 influence on atopic dermatitis occurrence. Postepy dermatologii i alergologii 7 35369616
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
2021 Association of BCL2 polymorphisms and the IL19 single nucleotide polymorphism rs2243188 with systemic lupus erythematosus. The Journal of international medical research 3 34044633
2020 IL-19 as a Biomarker for the Severity of Acute Myocardial Infarction. Archives of medical research 3 32111500
2000 Intratumoral IL-12 gene transfer improves the therapeutic efficacy of IL-12 but not IL-19. Folia biologica 3 11055798
2015 Immunogenetic influences on acquisition of HIV-1 infection: consensus findings from two African cohorts point to an enhancer element in IL19 (1q32.2). Genes and immunity 2 25633979
2012 IL-19 and IL-20 genes polymorphisms and haplotype analysis in a vesicoureteral reflux population. Human immunology 2 23000500
2001 Functional analysis of regulatory elements controlling the expression of the ecdysone-regulated Drosophila ng-1 gene. Mechanisms of development 2 11118881
2025 The signature based on interleukin family and receptors identified IL19 and IL20RA in promoting nephroblastoma progression through STAT3 pathway. Scientific reports 1 40185911
2025 IL-19 Is a Novel Lymphangiocrine Factor Inducing Lymphangiogenesis and Lymphatic Junctional Regulation. Arteriosclerosis, thrombosis, and vascular biology 1 40371466
2025 Role of serum interleukin-19 (IL-19) levels in acne vulgaris: a comprehensive case control study. Archives of dermatological research 1 40372535
2025 TOPK Drives IL19-Mediated Crosstalk Between Cancer Cells and Fibroblasts to Promote Solar UV-Induced Skin Damage and Carcinogenesis. Cancers 1 40647365
2025 IL-19 suppresses Hippo signaling via modulating YAP1 phosphorylation in osteoarthritis. Frontiers in immunology 1 41103413
2024 Immunohistochemical Analysis of IL-19 and IL-24 Expression in Inflammatory Bowel Disease (IBD) Patients: Results From a Single Center Retrospective Study. Cureus 1 39007024
2016 [Association between IL-19 gene polymorphisms and hepatitis B virus susceptibility in children]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 1 27974122
2026 [The significance of IL-19 in the liver: crosstalk among inflammation, metabolism, and fibrosis]. Nihon yakurigaku zasshi. Folia pharmacologica Japonica 0 41485927
2026 Molecular characterization and functional analysis of IL-19 like in large yellow croaker (Larimichthys crocea). Developmental and comparative immunology 0 41831327
2026 IL-19 promotes psoriasis progression by inhibiting keratinocyte apoptosis via the Bcl-2/Caspase-3 axis. International immunopharmacology 0 42155391
2025 Assessment of Serum and Saliva CRP, IL-17, and IL-19 Levels in Patients with Different Severity of Acne Vulgaris. International journal of molecular sciences 0 41465543
2023 Functional role of IL-19 in a mouse model of L-arginine-induced pancreatitis and related lung injury. Experimental animals 0 38057085
2021 [Therapeutic application utilizing the anti-inflammatory effect of IL-19]. Nihon yakurigaku zasshi. Folia pharmacologica Japonica 0 34470933
2015 [Increased IL-19 level in peripheral blood of patients with allergic rhinitis is related with clinical severity]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 26522365

Missed literature

Know a paper Affinage missed for IL19? Flag it for the maintainers and the community.

No submissions yet.