Affinage

IL1RL2

Interleukin-1 receptor-like 2 · UniProt Q9HB29

Length
575 aa
Mass
65.4 kDa
Annotated
2026-04-28
39 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL1RL2 (IL-36R) is a single-pass transmembrane receptor of the IL-1 receptor family that functions as the primary signaling receptor for IL-36α, IL-36β, and IL-36γ cytokines at epithelial barrier surfaces and in hematopoietic cells, driving innate and adaptive proinflammatory responses. IL-36 ligands bind IL-36R with low affinity, enabling high-affinity recruitment of the obligate co-receptor IL-1RAcP to form a heterodimeric signaling complex that activates MyD88-dependent NF-κB and MAPK (JNK, ERK1/2, p38) cascades, inducing production of IL-6, IL-12, IL-23, chemokines, and antimicrobial peptides in keratinocytes, dendritic cells, fibroblasts, CD4+ T cells, neutrophils, and astrocytes (PMID:14734551, PMID:21860022, PMID:32239732). Receptor activity is antagonized by IL-36Ra, IL-38, and a soluble IL-36R isoform whose generation is controlled by DDX5-dependent pre-mRNA splicing; therapeutic antibodies such as spesolimab act as allosteric antagonists by binding the Ig1/Ig2 ectodomains remote from the ligand-binding site, preventing IL-1RAcP recruitment (PMID:36271146, PMID:32239732). IL-36R signaling is essential for mucosal defense against enteric pathogens via DC-derived IL-23/IL-6 driving IL-22 from ILC3s and T cells, for wound healing in the intestinal epithelium, and for neutrophil-mediated tumor killing; conversely, excessive IL-36R activity promotes psoriatic skin inflammation, intestinal pathology, and skeletal muscle atrophy, and homozygous human IL1RL2 loss-of-function demonstrates the receptor is dispensable for broad immune competence (PMID:33087566, PMID:26783184, PMID:29021166, PMID:37317970).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 High

    Mapping IL1RL2 to chromosome 2q12 within a conserved IL-1 receptor gene cluster established its evolutionary relationship to the IL-1R family, framing subsequent ligand-identification efforts.

    Evidence PAC contig construction and radiation hybrid mapping of the 2q12 locus

    PMID:10191101

    Open questions at the time
    • No ligand or signaling function yet identified
    • Expression pattern unknown
  2. 2003 Medium

    Detection of IL-1Rrp2 mRNA in brain astrocytes and microglia but not neurons, together with the unexpected failure of IL-1F9 to trigger classical NF-κB/MAPK signaling in these cells, raised the question of whether IL-1Rrp2 uses a distinct downstream pathway in the CNS.

    Evidence RT-PCR, NF-κB/MAPK activation assays, and IL-6 ELISA in primary mouse brain cells; intracerebroventricular injection in rat

    PMID:12799018

    Open questions at the time
    • No co-receptor requirement tested
    • Alternative signaling pathways not identified
    • Single-lab observation
  3. 2004 High

    Demonstrating that IL-1F6, IL-1F8, and IL-1F9 all signal through IL-1Rrp2 plus the co-receptor IL-1RAcP to activate NF-κB and MAPKs solved the core receptor-usage question for these orphan IL-1 family cytokines.

    Evidence NF-κB reporter assays, receptor-blocking antibodies, dominant-negative IL-1RAcP, MAPK activation, cytokine secretion in Jurkat and NCI/ADR-RES cells

    PMID:14734551

    Open questions at the time
    • Binding affinities for individual ligands unknown
    • Structural basis of ligand recognition unresolved
    • Cell-type-specific expression and function not yet explored
  4. 2011 High

    Extending IL-36R function to dendritic cells and CD4+ T cells revealed the receptor bridges innate and adaptive immunity by inducing IL-12, IL-23, and T cell cytokines (IFN-γ, IL-4, IL-17), and established that IL-36Ra acts as a competitive antagonist at high molar excess.

    Evidence Cytokine stimulation of primary murine BMDCs and CD4+ T cells with ELISA and flow cytometry readouts; in vivo immunization

    PMID:21860022

    Open questions at the time
    • Mechanism of IL-36Ra antagonism not structurally resolved
    • Threshold for IL-36Ra inhibition in vivo unclear
  5. 2012 High

    Showing that IL-1Rrp2 expression in the human myelomonocytic lineage is restricted to dendritic cells and upregulated by IL-4, and that IL-36 ligands drive DC maturation and Th1 polarization, defined the receptor's role in shaping adaptive immune responses at barrier surfaces.

    Evidence RT-PCR, flow cytometry, ELISA, and lymphocyte proliferation assays in primary human MDDCs and pDCs

    PMID:22144259

    Open questions at the time
    • Regulation of receptor expression on other cell types not addressed
    • Signaling downstream of receptor in DCs not dissected
  6. 2016 High

    IL-36R-deficient mice revealed an essential protective role in intestinal epithelial homeostasis — activating fibroblasts, inducing antimicrobial lipocalin-2, and promoting epithelial proliferation via MyD88 — answering whether IL-36R contributes to mucosal defense beyond skin.

    Evidence Il1rl2 knockout and MyD88-deficient mice in DSS colitis and wound healing models; neutralizing antibodies; RNA-seq

    PMID:26783184

    Open questions at the time
    • Specific IL-36 ligand(s) responsible in intestine not identified
    • Epithelial vs. immune cell-intrinsic contributions not separated
  7. 2017 High

    Anti-IL-36R antibody blockade reduced psoriatic inflammation in human skin, and characterization of human IL1RL2 loss-of-function individuals showed preserved broad immune function, validating IL-36R as a safe therapeutic target for inflammatory skin disease.

    Evidence Transcriptomics of stimulated keratinocytes; ex vivo/in vivo IL-36R blockade in psoriatic skin; phenotyping of homozygous IL1RL2 KO humans

    PMID:28726542 PMID:29021166

    Open questions at the time
    • Long-term consequences of IL-36R absence not assessed
    • Whether IL-36R KO humans have subtle barrier defects not fully excluded
  8. 2019 High

    Placing IL-36R downstream of TLR4 in NET-driven psoriatic inflammation via MyD88/NF-κB established crosstalk between innate danger signals and IL-36R-mediated amplification loops in skin pathology.

    Evidence IMQ-induced psoriasis mouse model with DNase I, TLR4 inhibition, and LCN2 neutralization

    PMID:31024570

    Open questions at the time
    • Whether NETs directly release IL-36 ligands or act indirectly not resolved
    • Relevance to human NET-driven disease not confirmed
  9. 2020 High

    Structural determination of the IL-36R ectodomain revealed that a therapeutic anti-IL-36R antibody binds the Ig1/Ig2 domains remote from both ligand- and IL-1RAcP-binding sites, establishing an allosteric mechanism of antagonism distinct from competitive blocking.

    Evidence X-ray crystallography at 2.3 Å resolution

    PMID:32239732

    Open questions at the time
    • Full ternary complex structure (IL-36R/ligand/IL-1RAcP) not yet solved at this time
    • Allosteric conformational change not directly visualized
  10. 2020 High

    IL-36R signaling in dendritic cells activates NF-κB-p65 to produce IL-6 and IL-23 that drive IL-22 from ILC3s and CD4+ T cells, providing the molecular pathway by which IL-36R integrates innate and adaptive mucosal defense against enteric infection.

    Evidence Il1rl2 KO mice infected with C. rodentium; cytokine rescue; genetic deletion of NF-κB-p65 and AhR

    PMID:33087566

    Open questions at the time
    • Whether this pathway operates identically in human gut not established
    • DC-intrinsic vs. bystander effects not fully separated
  11. 2022 High

    Discovery that DDX5-dependent pre-mRNA splicing controls the ratio of membrane-bound to soluble IL-36R, regulated upstream by IL-17D/CD93/p38/AKT/SMAD2/3, uncovered a post-transcriptional mechanism that tunes IL-36R signal strength in keratinocytes.

    Evidence Keratinocyte-specific Ddx5 KO mice; RNA splicing analysis; rescue with sIL-36R in atopic dermatitis and psoriasis models

    PMID:36271146

    Open questions at the time
    • Whether DDX5-dependent splicing regulation occurs in non-keratinocyte cells unknown
    • Direct DDX5 binding to IL1RL2 pre-mRNA splice sites not shown
  12. 2023 Medium

    IL-36R signaling in hematopoietic cells, particularly neutrophils, cell-intrinsically enhances direct tumor killing and promotes anti-tumor T and NK cell responses, extending IL-36R function to cancer immunosurveillance.

    Evidence Il1rl2-deficient mice with hematopoietic cell transfer in tumor models; neutrophil functional assays

    PMID:37317970

    Open questions at the time
    • Molecular effectors downstream of IL-36R in neutrophil tumoricidal function not identified
    • Human relevance not demonstrated
    • Single-lab finding
  13. 2024 Medium

    Reporter mouse imaging resolved IL-36R expression to outward-facing epithelial barriers (skin, oral mucosa, esophagus, upper airways) but not inward-facing epithelia (alveoli, small intestine, colon), while leukocytes in all barrier tissues express IL-36R, clarifying the receptor's tissue tropism.

    Evidence Cre-dependent mCherry reporter mouse strain with fluorescence imaging across barrier tissues

    PMID:38727323

    Open questions at the time
    • Protein-level validation beyond reporter not performed
    • Dynamic regulation of expression under inflammatory conditions not tested
    • Single-lab finding
  14. 2025 Medium

    IL-36R signaling in skeletal muscle cells drives NF-κB-p65-dependent upregulation of the E3 ubiquitin ligases FBXO32 and TRIM63, linking IL-36R to muscle atrophy — the first non-barrier, non-immune tissue function described.

    Evidence Il1rl2 KO mice exposed to cigarette smoke; C2C12 myotube stimulation; NF-κB signaling and western blot

    PMID:40773893

    Open questions at the time
    • Whether IL-36R is expressed on skeletal muscle in humans not confirmed
    • Single-lab finding
    • Contribution of systemic inflammation vs. direct muscle IL-36R signaling not fully delineated

Open questions

Synthesis pass · forward-looking unresolved questions
  • A complete ternary structure of IL-36R/IL-36 ligand/IL-1RAcP at high resolution, the structural basis for differential ligand potency among IL-36α/β/γ, the cell-intrinsic signaling cascade downstream of IL-36R in neutrophils, and the human in vivo relevance of the DDX5-sIL-36R regulatory axis remain unresolved.
  • Full ternary complex structure at atomic resolution still needed
  • Ligand-specific signaling differences through the same receptor unexplained
  • DDX5-dependent splicing regulation of IL1RL2 not validated in human tissue

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 5
Partners
DDX5IL1RAPIL36AIL36BIL36GIL36RNIL38MYD88
Complex memberships
IL-36R/IL-1RAcP heterodimer

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 IL-1F6 (IL-36α), IL-1F8 (IL-36β), and IL-1F9 (IL-36γ) signal through IL-1Rrp2 (IL1RL2) and the co-receptor IL-1RAcP to activate NF-κB and MAPKs (JNK, ERK1/2); antibody blockade of IL-1RAcP and transfection of cytoplasmically-deleted IL-1RAcP both blocked NF-κB activation, establishing that both receptor chains are required for signaling. NF-κB reporter assays in Jurkat and NCI/ADR-RES cells, receptor-blocking antibodies, dominant-negative IL-1RAcP transfection, MAPK activation assays, IL-6 and IL-8 secretion assays The Journal of biological chemistry High 14734551
1999 IL1RL2 gene is located on human chromosome 2q12 within a cluster of IL-1 receptor family genes (order cen→tel: IL1R2, IL1R1, IL1RL2, IL1RL1, IL18R1) within a 530 kb contig; all genes are transcribed in the same direction. PAC clone contig construction, radiation hybrid mapping Genomics High 10191101
2011 IL-36R (IL1RL2) and IL-1RAcP form the functional receptor complex for IL-36α, IL-36β, and IL-36γ on murine bone marrow-derived dendritic cells and CD4+ T lymphocytes, activating production of proinflammatory cytokines (IL-12, IL-1β, IL-6, TNF-α, IL-23) and T cell cytokines (IFN-γ, IL-4, IL-17); IL-36Ra antagonized these effects at 100–1000-fold molar excess. Cytokine stimulation of primary murine BMDCs and CD4+ T cells, ELISA, flow cytometry for co-stimulatory molecules, in vivo immunization with IL-36β Blood High 21860022
2012 IL-1Rrp2 (IL1RL2) expression within the human myelomonocytic lineage is unique to dendritic cells; IL-4 dose-dependently upregulates IL-1Rrp2 on monocyte-derived DCs; IL-1F8 or IL-1F9 signaling through IL-1Rrp2 induces MDDC maturation (increased HLA-DR, CD83, CD40, CD80; decreased CD1a) and IL-12p70 and IL-18 secretion, promoting Th1 lymphocyte proliferation. RT-PCR, flow cytometry, ELISA, lymphocyte proliferation assay using primary human MDDCs and plasmacytoid DCs European journal of immunology High 22144259
2016 IL-36R (IL1RL2) signaling via MyD88 activates colonic fibroblasts to produce chemokines, GM-CSF, and IL-6, and induces proliferation of intestinal epithelial cells and expression of antimicrobial lipocalin-2; IL-36R-deficient mice show high susceptibility to DSS colitis and impaired wound healing. IL-36R-/- and MyD88-deficient mouse models, DSS colitis and wound healing models in vivo, neutralizing anti-IL-36R antibodies, recombinant IL-36R ligands, RNA-seq genome expression analysis Gut High 26783184
2017 IL-36R (IL1RL2) blockade with neutralizing antibody or recombinant antagonist markedly reduces IL-17 expression, keratinocyte activation, and leukocyte infiltration in psoriatic skin; loss-of-function IL1RL2 knockout in humans preserves broad immune function, validating IL-36R as a therapeutic target. Transcriptomics of primary human keratinocytes stimulated with IL-36 cytokines, ex vivo and in vivo IL-36R blockade in psoriatic skin, phenotyping of individuals with homozygous IL1RL2 knockout mutations Science translational medicine High 29021166
2017 An antagonistic anti-human IL-36R monoclonal antibody (MAB92) binds primarily to domain-2 of the IL-36R extracellular region and blocks all three IL-36 ligand (α, β, γ)-mediated signaling in primary human keratinocytes and dermal fibroblasts; a mouse cross-reactive surrogate antibody (MAB04) abrogates imiquimod- and IL-36-mediated skin inflammation in vivo. In vitro signaling inhibition assays, epitope mapping, imiquimod mouse model of skin inflammation, primary keratinocyte and fibroblast cytokine production assays mAbs High 28726542
2020 X-ray crystal structure of human IL-36R extracellular domain in complex with an anti-IL-36R Fab at 2.3 Å resolution reveals that the antibody epitope is located on Ig1 and Ig2 domains, remote from both the putative ligand and accessory protein (IL-1RAcP) binding interfaces, indicating the antibody acts as an allosteric (non-competitive) antagonist. X-ray crystallography at 2.3 Å resolution Protein science High 32239732
2019 NETs drive inflammatory responses in skin through TLR4/IL-36R crosstalk and MyD88/NF-κB downstream signaling; IL-36R (encoded by Il1rl2) is required for NET-induced proinflammatory activity including LCN2 induction, as shown in the IMQ-induced psoriasis model. IMQ-induced psoriasis mouse model, DNase I/CI-amidine treatment in vivo, TLR4 inhibition, LCN2 neutralization, K14-VEGF transgenic mice Frontiers in immunology High 31024570
2022 IL-17D downregulates DDX5 expression in keratinocytes via the CD93-p38 MAPK-AKT-SMAD2/3 signaling pathway, causing pre-mRNA splicing to favor membrane-bound full-length IL-36R over soluble IL-36R (sIL-36R), thereby selectively amplifying IL-36R-mediated inflammatory responses; restoration of sIL-36R suppresses skin inflammation in Ddx5ΔKC mice. Keratinocyte-specific Ddx5 knockout mice, RNA splicing analysis, cytokine pathway signaling assays, experimental atopic dermatitis and psoriasis models in vivo Nature immunology High 36271146
2020 IL-36R (Il1rl2)-deficient mice show impaired IL-22 and antimicrobial peptide (AMP) expression, increased intestinal damage, and failure to control C. rodentium infection; IL-36R signaling in dendritic cells activates NFκB-p65 to produce IL-6 and IL-23, which drive IL-22 production from ILC3s and CD4+ T cells (via AhR) respectively, integrating innate and adaptive immunity. Il1rl2 knockout mice, C. rodentium infection model, cytokine rescue experiments (IL-23, IL-6 administration), intracellular cytokine staining, genetic deletion of NFκB-p65 and AhR Proceedings of the National Academy of Sciences of the United States of America High 33087566
2018 Spinal IL-36R (IL1RL2) is expressed primarily on astrocytes; neuronal IL-36γ activates IL-36R on astrocytes to trigger JNK phosphorylation and release of inflammatory cytokines, which is sufficient to induce mechanical allodynia and thermal hyperalgesia; blocking JNK or IL-36R signaling attenuates CFA-induced chronic inflammatory pain. CFA chronic inflammatory pain model in mice, intrathecal IL-36R antagonist and siRNA administration, in vitro astrocyte stimulation assays, JNK inhibitor (pharmacological), pain behavior testing Glia Medium 30578562
2003 IL-1Rrp2 (IL1RL2) mRNA is expressed constitutively in mouse brain astrocytes and microglia but not primary neurons; LPS strongly decreases IL-1Rrp2 expression in glial cells; despite receptor expression, IL-1F9 fails to induce classical IL-1β signaling responses (NF-κB, MAPKs, IL-6 release, fever) in glial cells or in vivo in rat, suggesting activation of alternative pathways. RT-PCR in primary mouse brain cells, NF-κB and MAPK activation assays, IL-6 ELISA, in vivo intracerebroventricular injection in rat Journal of neuroimmunology Medium 12799018
2020 Enhanced IL-36R (IL1RL2) signaling (DITRA-like humanized mice) promotes tissue pathology during intestinal injury and impairs mucosal restoration in the repair phase of DSS-induced chronic colitis; anti-IL-36R antibody blockade ameliorates DSS-induced intestinal inflammation and rescues mucosal recovery in vivo. Humanized DITRA-like mouse model, DSS-induced colitis, in vivo anti-IL-36R antibody treatment (prophylactic and therapeutic), imiquimod skin inflammation model Science immunology High 33443029
2022 IL-36γ signaling through IL-36R (IL1RL2) in breast cancer and epidermal cells activates MEK1/2, ERK1/2, JNK1/2, and c-Jun phosphorylation, leading to increased AP-1 activity and enhanced cell proliferation and anchorage-independent growth; PIN1 further amplifies IL-36γ-induced tumorigenic capacity via MEK/ERK and JNK/c-Jun signaling. BrdU incorporation, anchorage-independent growth assays, western blotting for MAPK phosphorylation, AP-1 reporter assays, PIN1 knockout syngeneic mouse tumor model Cancers Medium 35954317
2023 IL-36 signaling through IL-36R (IL1RL2) on host hematopoietic cells modulates neutrophils in a cell-intrinsic manner to enhance direct tumor killing and promote T and NK cell responses, remodeling an immunosuppressive tumor microenvironment. Il1rl2-deficient mice, hematopoietic cell transfer experiments, in vivo tumor models, neutrophil functional assays for tumor killing The Journal of clinical investigation Medium 37317970
2023 IL-38 suppresses abdominal aortic aneurysm formation by binding IL1RL2 (IL-36R) on macrophages and inhibiting p38 phosphorylation, thereby reducing M1 macrophage accumulation and MMP-2/MMP-9 expression in the aortic wall; p38 inhibition (SB203580) abolished IL-38's protective effects, confirming dependence on the IL-36R/p38 pathway. Angiotensin II-induced mouse AAA model, IL-38 treatment, RAW264.7 cell stimulation assays, p38 inhibitor (SB203580), western blot for phospho-p38, MMP activity assays Physiological reports Medium 36708509
2025 S. aureus epicutaneous exposure promotes neutrophilic lung inflammation via keratinocyte- and lung epithelia-specific IL-36R signaling; neutrophil IL-36R signaling additionally triggers neutrophil extracellular trap (NET) formation to augment lung pathology; anti-IL-36R monoclonal antibody treatment prevented neutrophilic lung inflammation. Preclinical atopic march mouse model, keratinocyte- and epithelium-specific IL-36R conditional knockouts, anti-IL-36R mAb treatment, NET quantification assays Cell reports Medium 40711876
2025 Cryo-EM/structural analysis reveals IL-36R engages IL-36γ with low affinity, enabling high-affinity recruitment of the co-receptor IL-1RAcP; IL-37 binds IL-36R via an opposite binding signature yet activates common pro-inflammatory signaling (though less potently than IL-36γ); spesolimab acts as an allosteric antagonist of IL-36R by binding in a manner that prevents IL-1RAcP recruitment without directly competing with cytokine binding. Structural biology (cryo-EM/crystal structures), binding affinity measurements, functional signaling assays comparing IL-36γ and IL-37, spesolimab epitope and mechanism characterization bioRxivpreprint High bio_10.1101_2025.02.22.639629
2025 IL-36/IL-36R (IL1RL2) signaling in skeletal muscle cells activates NF-κB p65 pathway to upregulate FBXO32 and TRIM63 (E3 ubiquitin ligases), leading to skeletal muscle atrophy; IL-36R deletion in mice attenuated cigarette smoke-induced skeletal muscle dysfunction alongside lung inflammation. IL-36R knockout mice, cigarette smoke exposure model, C2C12 myotube stimulation, NF-κB signaling assays, western blot for FBXO32/TRIM63 International immunopharmacology Medium 40773893
2024 IL-1RL2 (IL-36R) mCherry reporter mice reveal that IL-1RL2 expression in barrier tissues is strong in epithelial cells directly exposed to the environment (skin, oral mucosa, esophagus, upper airways) but nearly absent from inward-facing epithelia (lung alveoli, small intestine, colon), while leukocytes in all barrier tissues express IL-1RL2. Cre-dependent mCherry reporter mouse strain (floxed Il1rl2 locus), fluorescence imaging of barrier tissues Cells Medium 38727323
2025 IL-36γ stimulation of naïve CD4+ T cells through IL-36R (IL1RL2) significantly induces IFNγ expression in vitro; in vivo, IL-36γ-stimulated CD4+ T cells cause augmented intestinal inflammation in the T cell transfer model of colitis; IFNγ-/- CD4+ T cells show dramatically reduced TNFα production, indicating IL-36R-driven IFNγ→TNFα cytokine network mediates colitis. Naive CD4+ T cell stimulation assays, ELISA, qPCR, T cell transfer model of colitis in Rag-/- mice, IFNγ-/- cells Frontiers in immunology Medium 40642091

Source papers

Stage 0 corpus · 39 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF-kappaB and MAPKs. The Journal of biological chemistry 346 14734551
2011 IL-36R ligands are potent regulators of dendritic and T cells. Blood 258 21860022
2019 Neutrophil Extracellular Traps Promote Inflammatory Responses in Psoriasis via Activating Epidermal TLR4/IL-36R Crosstalk. Frontiers in immunology 164 31024570
2016 IL-36R signalling activates intestinal epithelial cells and fibroblasts and promotes mucosal healing in vivo. Gut 156 26783184
2017 An analysis of IL-36 signature genes and individuals with IL1RL2 knockout mutations validates IL-36 as a psoriasis therapeutic target. Science translational medicine 133 29021166
2010 IL-1RL2 and its ligands contribute to the cytokine network in psoriasis. Journal of immunology (Baltimore, Md. : 1950) 127 20833839
2019 The Significance of IL-36 Hyperactivation and IL-36R Targeting in Psoriasis. International journal of molecular sciences 121 31284527
1999 Interleukin-1 receptor cluster: gene organization of IL1R2, IL1R1, IL1RL2 (IL-1Rrp2), IL1RL1 (T1/ST2), and IL18R1 (IL-1Rrp) on human chromosome 2q. Genomics 88 10191101
2012 Expression of IL-1Rrp2 by human myelomonocytic cells is unique to DCs and facilitates DC maturation by IL-1F8 and IL-1F9. European journal of immunology 83 22144259
2017 Generation and functional characterization of anti-human and anti-mouse IL-36R antagonist monoclonal antibodies. mAbs 71 28726542
2022 IL-17D-induced inhibition of DDX5 expression in keratinocytes amplifies IL-36R-mediated skin inflammation. Nature immunology 70 36271146
2024 Emerging Role of the IL-36/IL-36R Axis in Multiple Inflammatory Skin Diseases. The Journal of investigative dermatology 36 38189700
2003 IL-1Rrp2 expression and IL-1F9 (IL-1H1) actions in brain cells. Journal of neuroimmunology 35 12799018
2018 Spinal IL-36γ/IL-36R participates in the maintenance of chronic inflammatory pain through astroglial JNK pathway. Glia 32 30578562
2020 Enhanced IL-36R signaling promotes barrier impairment and inflammation in skin and intestine. Science immunology 29 33443029
2020 IL-36R signaling integrates innate and adaptive immune-mediated protection against enteropathogenic bacteria. Proceedings of the National Academy of Sciences of the United States of America 20 33087566
2022 IL-36 signalling enhances a pro-tumorigenic phenotype in colon cancer cells with cancer cell growth restricted by administration of the IL-36R antagonist. Oncogene 17 35365751
2014 Anti-IL-36R antibodies, potentially useful for the treatment of psoriasis: a patent evaluation of WO2013074569. Expert opinion on therapeutic patents 17 24456078
2016 Altered expression of IL36γ and IL36 receptor (IL1RL2) in the colon of patients with Hirschsprung's disease. Pediatric surgery international 16 27853811
2023 Autonomous IL-36R signaling in neutrophils activates potent antitumor effector functions. The Journal of clinical investigation 13 37317970
2022 The Protective Role of IL-36/IL-36R Signal in Con A-Induced Acute Hepatitis. Journal of immunology (Baltimore, Md. : 1950) 12 35046104
2021 IL-36α Exerts Proinflammatory Effects in Aspergillus fumigatus Keratitis of Mice Through the Pathway of IL-36α/IL-36R/NF-κB. Investigative ophthalmology & visual science 11 33851975
2021 Role of IL-36γ/IL-36R Signaling in Corneal Innate Defense Against Candida albicans Keratitis. Investigative ophthalmology & visual science 10 33970198
2024 Spesolimab, the first-in-class anti-IL-36R antibody: From bench to clinic. The Journal of dermatology 9 39373152
2022 Regulation of Interleukin-36γ/IL-36R Signaling Axis by PIN1 in Epithelial Cell Transformation and Breast Tumorigenesis. Cancers 8 35954317
2021 Proteomic and molecular evidences of Il1rl2, Ric8a, Krt18 and Hsp90b1 modulation during experimental hepatic fibrosis and pomegranate supplementation. International journal of biological macromolecules 8 34174316
2023 Interleukin-38 suppresses abdominal aortic aneurysm formation in mice by regulating macrophages in an IL1RL2-p38 pathway-dependent manner. Physiological reports 7 36708509
2020 X-ray crystal structure localizes the mechanism of inhibition of an IL-36R antagonist monoclonal antibody to interaction with Ig1 and Ig2 extra cellular domains. Protein science : a publication of the Protein Society 7 32239732
2019 Retrospective analysis of model-based predictivity of human pharmacokinetics for anti-IL-36R monoclonal antibody MAB92 using a rat anti-mouse IL-36R monoclonal antibody and RNA expression data (FANTOM5). mAbs 7 31068073
2024 Casting NETs on Psoriasis: The modulation of inflammatory feedback targeting IL-36/IL-36R axis. International immunopharmacology 6 39306890
2020 Preclinical characterization of the ADME properties of a surrogate anti-IL-36R monoclonal antibody antagonist in mouse serum and tissues. mAbs 6 32310023
2025 IL-36/IL-36R signaling promotes CD4+ T cell-dependent colitis via pro-inflammatory cytokine production. Frontiers in immunology 2 40642091
2025 Epicutaneous Staphylococcus aureus initiates cross-tissue IL-36R signaling for neutrophilic lung inflammation in a model of the atopic march. Cell reports 2 40711876
2024 Floxed Il1rl2 Locus with mCherry Reporter Element Reveals Distinct Expression Patterns of the IL-36 Receptor in Barrier Tissues. Cells 2 38727323
2025 IL-36R deletion mitigates cigarette smoke-induced airway inflammation and skeletal muscle dysfunction. International immunopharmacology 1 40773893
2023 IL-36/IL-36R Signaling Promotes CD4+ T Cell-Dependent Colitis via Pro-Inflammatory Cytokine Production. bioRxiv : the preprint server for biology 1 37292643
2026 Aged skin exacerbates experimental osteoarthritis via enhanced IL-36R signaling. Nature communications 0 41530151
2026 Inhibitory effect of Anwulignan on the IL-36R/TLR9 signaling pathway: potential therapeutic role in hepatic fibrosis. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 41702259
2025 Serum Dysregulation of IL-36, IL-37, and IL-38 in Pyoderma Gangrenosum: Clinical Correlations and Implications for IL-36R-Targeted Therapy. International journal of molecular sciences 0 41465501