Affinage

IL17RA

Interleukin-17 receptor A · UniProt Q96F46

Length
866 aa
Mass
96.1 kDa
Annotated
2026-06-10
100 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL17RA is a shared receptor subunit that nucleates signaling for multiple IL-17 family cytokines by pairing with distinct co-receptors—IL-17RC for IL-17A, IL-17F, and the IL-17A/F heterodimer (PMID:18684971, PMID:21109515), IL-17RB for IL-25/IL-17E and IL-17B (PMID:18768888, PMID:30770417), and IL-17RE for IL-17C (PMID:38470486, PMID:23834281). Cytokine binding drives IL-17RA dimerization and assembly of a 2:2:2 hexameric IL-17RA/IL-17RC/IL-17A signalosome, and dimerization-defective IL-17RA mutants lose downstream gene induction (PMID:36260993); structural studies of IL-17RC bound to IL-17F reveal a competing 2:1 cytokine-binding geometry (PMID:32187518). Signal transduction requires an extended SEFIR+TILL intracellular module whose CC' loop directly binds the adaptor Act1, an interaction necessary for TRAF6 ubiquitination and downstream output (PMID:20729198, PMID:22045852), with RKIP acting as a positive scaffold that stabilizes the IL-17RA–Act1 complex (PMID:29674348). Engagement activates NF-κB, AP-1, and the ERK/p38/JNK MAPK cascades to drive chemokine and cytokine programs (IL-6, IL-8, CCL20, ELR+ CXC chemokines, MMPs) (PMID:21109515, PMID:17644350, PMID:18097068), with context-specific use of STAT3/JAK2 in fibroblasts (PMID:28898718, PMID:30604628), Rab35/PKCα-fascin in airway smooth muscle (PMID:30683702), and Syk in macrophages (PMID:40023157). Through these pathways IL17RA governs barrier and tissue physiology, including neutrophil recruitment to lung (PMID:19783685, PMID:26871571), intestinal secretory-lineage commitment via ATOH1 (PMID:35081371), control of microbiota and gut-liver immunity (PMID:31747600), and tumor-suppressive epithelial and macrophage functions in colorectal cancer (PMID:40023157). Complete autosomal recessive IL17RA deficiency in humans abolishes responses to IL-17A/F and IL-25 and causes chronic mucocutaneous candidiasis and staphylococcal infection, establishing its non-redundant role in mucocutaneous immunity (PMID:27930337).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2008 High

    Established that IL17RA is not a solitary receptor but functions in obligate heteromeric complexes with co-receptors to read distinct IL-17 family ligands.

    Evidence siRNA knockdown plus SPR binding for IL-17A/F via IL-17RA/IL-17RC, and KO mice plus blocking antibody for IL-25 via IL-17RA/IL-17RB

    PMID:18684971 PMID:18768888

    Open questions at the time
    • Stoichiometry of the assembled complexes not resolved
    • Mechanism coupling ligand binding to intracellular signaling not addressed
  2. 2011 High

    Defined the molecular basis of intracellular signal initiation by mapping the Act1-binding determinant to the CC' loop of an extended SEFIR+TILL domain, distinguishing receptor engagement from downstream output.

    Evidence Structure-function deletion mutagenesis, SPR with CC' loop peptide, and a cell-permeable decoy peptide blocking signaling in vitro and in vivo

    PMID:20729198 PMID:22045852

    Open questions at the time
    • Atomic structure of the SEFIR-SEFIR interface not determined
    • How TRAF6 ubiquitination is mechanistically licensed downstream of Act1 not fully resolved
  3. 2007 Medium

    Showed that the IL17RA/IL-17RC pair converges on NF-κB, AP-1, and ERK/p38/JNK MAPK to drive chemokine and inflammatory cytokine programs across epithelial and stromal cell types.

    Evidence siRNA knockdown of either receptor with MAPK Western blotting, transcription factor activation assays, ELISA, and microarray in synoviocytes, gastric cells, and airway smooth muscle

    PMID:15893694 PMID:17644350 PMID:18097068 PMID:21109515

    Open questions at the time
    • Relative contributions of each MAPK branch to specific gene targets not dissected
    • Cell-type determinants of pathway selection unclear
  4. 2020 High

    Resolved the architecture of the signaling-competent receptor, revealing ligand-induced IL17RA dimerization into a 2:2:2 hexamer and an alternative IL-17RC-centered 2:1 geometry, linking assembly to function.

    Evidence X-ray crystallography of IL-17RA/IL-17RC ectodomains with IL-17A/IL-17F, biophysical binding, and dimerization-defective mutants tested in keratinocytes

    PMID:32187518 PMID:36260993

    Open questions at the time
    • Whether IL-17RA-independent IL-17RC signaling occurs in cells not directly demonstrated
    • Conformational coupling from ectodomain assembly to intracellular SEFIR not visualized
  5. 2018 Medium

    Identified positive and small-molecule modulators of the IL17RA–Act1 axis, expanding the regulatory and pharmacological control points of the receptor.

    Evidence Co-IP and KO/EAE for RKIP as a scaffold; structure-based and SPR/pull-down identification of cyanidin, HAP peptide, and gingerenone A blocking the IL-17A/IL17RA interface

    PMID:27184415 PMID:28223414 PMID:29674348 PMID:38639442

    Open questions at the time
    • Endogenous regulation of RKIP-IL17RA coupling in human disease not established
    • Inhibitor specificity versus other IL-17 family receptors not fully delineated
  6. 2022 High

    Revealed cell-type-specific, non-canonical IL17RA signaling outputs beyond NF-κB/MAPK, including cytoskeletal, metabolic, and differentiation programs.

    Evidence Conditional KO and co-IP for Rab35/PKCα-fascin in airway smooth muscle, STAT3/JAK2 axes in fibroblasts, STAT3/FABP4 in ovarian cancer, and ATOH1 induction in intestinal stem cells/organoids

    PMID:30604628 PMID:30683702 PMID:31802182 PMID:35081371

    Open questions at the time
    • How a single receptor selects among these divergent outputs is unresolved
    • Direct biochemical links from IL17RA to JAK2/STAT3 not fully mapped
  7. 2019 High

    Demonstrated tissue-protective and barrier functions of IL17RA in epithelial and stromal compartments, including microbiota control, gut-liver immunity, and tumor suppression.

    Evidence Tissue-specific conditional KO with 16S sequencing, hepatitis and colorectal tumor models, Syk activation assays, and bacterial/viral challenge models

    PMID:19783685 PMID:26871571 PMID:29760692 PMID:31747600 PMID:34516780 PMID:40023157

    Open questions at the time
    • Compartment-specific signaling mechanisms not uniformly defined
    • Translation of protective epithelial roles to human disease incompletely characterized
  8. 2016 High

    Established the non-redundant human in vivo function of IL17RA by showing that biallelic loss-of-function abolishes responses to IL-17A/F and IL-25 and causes mucocutaneous infection susceptibility.

    Evidence Genetic analysis of 21 patients with surface expression flow cytometry and functional IL-17 response assays in fibroblasts and leukocytes

    PMID:27930337

    Open questions at the time
    • Genotype-phenotype variation across alleles not fully explained
    • Contribution of individual ligand pathways to specific clinical features not separated
  9. 2022 Medium

    Identified post-transcriptional and isoform-level regulation of IL17RA abundance as a control point in chronic inflammation.

    Evidence MeRIP-seq with FTO knockdown/overexpression in liver injury models, and RT-PCR/Western detection of a soluble splice isoform lacking the transmembrane domain

    PMID:24084331 PMID:36172147

    Open questions at the time
    • Functional role of the soluble isoform (decoy vs. agonist) not tested
    • Physiological triggers of FTO-mediated IL17RA regulation unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single shared receptor subunit selects among NF-κB/MAPK, STAT3, cytoskeletal, and differentiation outputs in a cell-type- and ligand-specific manner remains unresolved.
  • No unified model linking co-receptor identity to downstream pathway choice
  • Structural basis of intracellular signalosome assembly in cells not determined
  • Function of the soluble IL17RA isoform unestablished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 4 GO:0060089 molecular transducer activity 4 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-1266738 Developmental Biology 2
Partners
IL17RBIL17RCIL17REPEBP1RAB35STAT3TRAF3IP2TRAF6
Complex memberships
IL-17R-Act1 signaling complexIL-17RA/IL-17RB receptor complexIL-17RA/IL-17RC receptor complexIL-17RA/IL-17RE receptor complex

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 IL-17F/IL-17A heterodimeric cytokine signals through the IL-17RA/IL-17RC receptor complex; surface plasmon resonance showed IL-17A and IL-17F bind IL-17RC with comparable affinities but bind IL-17RA with different affinities; siRNA knockdown of IL-17RA or IL-17RC abolished heterodimer activity in bronchial epithelial cells. siRNA knockdown, surface plasmon resonance (SPR), functional cytokine assay Journal of immunology High 18684971
2008 IL-25 (IL-17E)-mediated activities require both IL-17RB and IL-17RA; splenocytes from IL-17RA KO mice failed to produce IL-5 or IL-13 in response to IL-25, and IL-17RA KO mice failed to respond to intranasal IL-25; blocking anti-IL-17RA mAb prevented IL-25 activity in human cells. Knockout mouse model, antagonistic antibody blockade, in vitro cytokine assay, in vivo pulmonary inflammation model Journal of immunology High 18768888
2010 IL-17RA signaling requires an extended SEFIR domain (termed SEFIR+TILL) beyond the previously defined SEFIR motif for downstream signaling; Act1 recruitment alone is not sufficient for signaling, but TRAF6 ubiquitination correlates tightly with functional receptors; deletion of the CC' loop (not the BB' loop) from IL-17RA abolished Act1-IL-17RA interaction. Structure-function mutagenesis, receptor deletion constructs, functional reporter assays, ubiquitination assays Journal of Biological Chemistry High 20729198
2011 The CC' loop of the SEFIR domain of IL-17RA is required for Act1 binding; SPR showed a CC' loop-based peptide directly binds IL-17RA; a cell-permeable CC' loop decoy peptide inhibited IL-17- and IL-25-mediated signaling in vitro and pulmonary inflammation in vivo. Surface plasmon resonance, deletion mutagenesis, cell-permeable decoy peptide in vitro and in vivo Science signaling High 22045852
2010 Both IL-17RA and IL-17RC are required for IL-17A- and IL-17F-induced NF-κB and MAPK (ERK, p38, JNK) activation and IL-6/IL-8/CCL20 secretion in human rheumatoid synoviocytes; siRNA silencing of either receptor nearly abolished IL-6 expression mediated by IL-17A. siRNA knockdown, MAPK western blotting, ELISA, microarray Annals of the rheumatic diseases Medium 21109515
2007 Both IL-17RA and IL-17RC are required for IL-17A-mediated activation of ERK, p38, JNK, AP-1, and p65 NF-κB in gastric adenocarcinoma cells; siRNA knockdown of either receptor nearly abolished IL-17A-induced c-Jun and p65 activation. siRNA knockdown, MAPK western blotting, transcription factor binding assay (TransAM), ELISA Cytokine Medium 17644350
2008 Both IL-17RA and IL-17RC are required for IL-17A-induced ELR+ CXC chemokine (CXCL1, CXCL5, CXCL6) expression in synoviocytes; siRNA silencing of either receptor reduced IL-17A-induced IL-6, IL-8, and CCL-20 secretion. siRNA knockdown, ELISA, microarray Journal of immunology Medium 18097068
2018 RKIP directly interacts with IL-17RA and Act1 to promote formation of the IL-17R-Act1 complex, resulting in enhanced MAPK and NF-κB activation and downstream cytokine production; RKIP deficiency in mice ameliorated EAE symptoms and reduced IL-17R-mediated proinflammatory responses. Co-immunoprecipitation, adoptive T cell transfer, KO mouse model, NF-κB/MAPK reporter assays EMBO reports Medium 29674348
2020 Crystal structure of the extracellular domain of human IL-17RC in complex with IL-17F revealed that IL-17RC forms a symmetrical 2:1 complex with IL-17F, competing with IL-17RA for cytokine binding; biophysical studies showed IL-17A and IL-17A/F heterodimer also form 2:1 complexes with IL-17RC, suggesting IL-17RA-independent signaling is possible. X-ray crystallography, biophysical binding assays (SPR/ITC) Immunity High 32187518
2022 IL-17A, IL-17F, and IL-17A/F induce IL-17RA dimerization; crystal structure of the extracellular domains of IL-17RA and IL-17RC in complex with IL-17A revealed a 2:2:2 hexameric signaling assembly; dimerization-defective IL-17RA mutants showed reduced IL-36γ and CXCL1 mRNA induction in human keratinocytes. X-ray crystallography, biophysical assays, mutagenesis, functional mRNA expression assay in keratinocytes Cell reports High 36260993
2017 Cyanidin specifically binds to an IL-17A binding site within IL-17RA (structure-based identification) and inhibits the IL-17A/IL-17RA interaction; this blocked IL-17A-induced skin hyperplasia and attenuated TH17-driven airway hyperreactivity in mice. Structure-based virtual screening, binding assays, in vivo murine models of psoriasis and asthma Science signaling Medium 28223414
2016 A 15-residue phage-display-derived peptide (HAP) binds IL-17A and blocks IL-17A/IL-17RA interaction; crystal structure revealed two HAP molecules bind one IL-17A dimer symmetrically with the C-terminal helix directly blocking the IL-17RA binding region of IL-17A. Phage display, saturation mutagenesis, X-ray crystallography, primary human cell functional assay Scientific reports High 27184415
2019 IL-17A/IL-17RA signaling promotes fatty acid uptake in ovarian cancer cells via the IL-17RA/p-STAT3/FABP4 axis; IL-17RA was required for IL-17A-induced STAT3 phosphorylation and FABP4 upregulation, promoting cellular palmitic acid uptake. In vitro cytokine stimulation, Western blotting, IL-17A-deficient mouse orthotopic model, siRNA knockdown Cancer immunology, immunotherapy Medium 31802182
2011 IL-17RA is required for CCL2 expression and MMP12 induction in response to cigarette smoke; IL-17RA-/- mice failed to develop emphysema after 6 months of cigarette smoke exposure, establishing IL-17RA signaling as necessary for smoke-induced COPD pathology. IL-17RA knockout mouse model, qPCR for CCL2 and MMP12, histological assessment of emphysema PloS one High 21647421
2009 IL-17RA signaling is required for neutrophil migration and myeloperoxidase increases in the lung after influenza infection; IL-17RA-/- mice showed reduced oxidized phospholipids and were protected from acute lung injury, but IL-17RA was dispensable for CD8+ T cell recruitment and viral clearance. IL-17RA knockout mouse model, flow cytometry, MPO assay, viral clearance assay, lipid oxidation assay Journal of immunology High 19783685
2013 IL-17RA is required for optimal localization of follicular Th (TFH) cells in the germinal center light zone; IL-17 signaling upregulates RGS16 in TFH cells to promote TFH-B cell conjugate formation; IL-17RA deficiency in BXD2 mice abrogated autoantibody-forming B cell generation without affecting total TFH numbers. IL-17RA knockout mouse (BXD2-Il17ra-/-), adenoviral IL-17R:Fc blockade, immunofluorescence, in vitro conjugate formation assay Journal of immunology Medium 23858031
2022 IL-17RA signaling in Lgr5+ intestinal stem cells induces ATOH1 transcription factor expression to promote secretory epithelial cell lineage commitment (Paneth, tuft, goblet, enteroendocrine cells); conditional deletion models showed IL-17RA signaling in ATOH1+ cells was required to regenerate secretory cells following injury; IL-17A stimulation of human intestinal organoids rescued secretory cell differentiation. Conditional knockout mouse models, human intestinal organoids, lineage tracing, immunofluorescence Immunity High 35081371
2019 IL-17A promotes airway smooth muscle contraction by recruiting Rab35 (via DennD1C GEF) to the IL-17R/Act1 complex, activating PKCα and phosphorylating fascin at Ser39, enabling F-actin/myosin stress fiber formation; cell-type-specific deletion of IL-17R or Act1 in airway smooth muscle cells confirmed direct role. Cell-type-specific conditional KO, co-immunoprecipitation, Rab35 knockdown, PKCα inhibitor, contraction assay Journal of immunology High 30683702
2022 FTO (a m6A demethylase) suppresses m6A mRNA methylation of IL-17RA, leading to increased IL-17RA expression; knockdown and overexpression of FTO in vitro and in vivo demonstrated FTO as the primary m6A modulator of IL-17RA, and increased IL-17RA promoted chronic hepatic inflammation. MeRIP-seq, FTO knockdown/overexpression, murine NAFLD/liver injury models, Western blotting Frontiers in oncology Medium 36172147
2013 A soluble isoform of human IL-17RA is generated by alternative splicing that removes exon 11 encoding the transmembrane domain; RT-PCR confirmed this variant in multiple human tissues and the secreted protein was detected in culture media by Western blotting. RT-PCR, Western blotting of conditioned media Cytokine Medium 24084331
2019 IL-17RA signaling in intestinal epithelial cells regulates microbial composition and constrains translocation of TLR9 ligands (CpG DNA); intestinal epithelium-specific IL-17RA deletion caused microbiome dysbiosis, increased CpG DNA translocation driving hepatic IL-18 production, and exacerbated immune-driven hepatitis. Intestinal epithelium-specific IL-17RA conditional KO mouse, 16S microbiome sequencing, hepatitis model, cytokine measurement Cell reports High 31747600
2017 IL-17 signaling in fibroblasts requires IL-17RA/STAT3 axis to induce SHP-2, Cyr61, IL-23, GM-CSF and RANKL expression in rheumatoid arthritis fibroblast-like synoviocytes; siRNA knockdown of IL-17RA reversed IL-17-induced RANKL expression and osteoclastogenic potential. siRNA knockdown, STAT3 inhibitor, co-culture osteoclastogenesis assay, Western blotting Molecular immunology Medium 28898718
2018 IL-17RA/Act1 signaling is required for IL-17R-induced lung immunity against Klebsiella; conditional deletion showed IL-17R signaling specifically in fibroblasts is required for lung-specific protective immunity (not systemic antibody-mediated protection) in a mucosal vaccine model. Cell-type-specific conditional IL-17R KO mouse, adoptive transfer, mucosal vaccine model, bacterial challenge Science immunology Medium 34516780
2019 IL-17RA signaling in non-hematopoietic cells controls CXCL-1 and CXCL-5 production to recruit neutrophils to the lung during the adaptive immune response to mycobacteria; CXCL-1 and CXCL-5 instillation reconstituted neutrophil recruitment in IL-17RA-/- mice. IL-17RA KO mouse, bone marrow transplantation, cytokine instillation rescue experiment, flow cytometry PloS one Medium 26871571
2024 Gingerenone A directly binds IL-17RA protein (confirmed by pull-down and SPR) and inhibits IL-17RA/Act1-mediated downstream signaling; lentivirus-mediated IL-17RA/Act1 knockdown impaired GA's protective effects against DSS-induced intestinal inflammation. Pull-down assay, surface plasmon resonance, molecular dynamics simulation, lentiviral knockdown, in vivo colitis model Advanced science Medium 38639442
2005 IL-17R (IL-17RA) is expressed on human airway smooth muscle (ASM) cells; IL-17 induces CXCL-8 production from ASM cells via a transcriptional mechanism dependent on NF-κB and AP-1 binding sites in the CXCL-8 promoter. Immunostaining, surface receptor detection, transcriptional inhibitor (actinomycin D), promoter reporter assay with site-directed mutation, neutralizing antibody Clinical immunology Medium 15893694
2016 Complete autosomal recessive IL-17RA deficiency in 21 patients abolished cellular responses to IL-17A/F homodimers and heterodimers in fibroblasts and to IL-17E/IL-25 in leukocytes; alleles creating premature stop codons upstream of the transmembrane domain prevented surface receptor expression, while those downstream or the missense D387N allele permitted surface expression but all abolished signaling. Patient genetic analysis, surface receptor expression by flow cytometry, functional IL-17 response assays in fibroblasts and leukocytes PNAS High 27930337
2019 IL-17A-induced fibrogenic response in lung fibroblasts is mediated through NF-κB signaling and requires JAK2 (but not JAK1/JAK3) downstream of IL-17RA; siRNA silencing of IL-17RA attenuated ECM production, myofibroblast transdifferentiation, and cell proliferation in response to IL-17A. siRNA knockdown, selective JAK inhibitors (AZD1480 vs. tofacitinib), Western blotting, proliferation and ECM assays American journal of physiology. Lung cellular and molecular physiology Medium 30604628
2019 IL-17RA signaling in Trypanosoma cruzi-infected mice is intrinsically required in CD8+ T cells for survival and effector function; IL-17A in vitro downregulated pro-apoptotic BAD and promoted activated CD8+ T cell survival; IL-17RA-deficient T. cruzi-specific CD8+ T cells showed increased apoptosis and dysfunction. IL-17RA KO mouse, adoptive transfer of IL-17RA-/- vs. WT T cells, in vitro recombinant IL-17 treatment, transcriptomic profiling, PD-L1 blockade Frontiers in immunology Medium 30364284
2025 IL-17RA in intestinal epithelial cells (IECs) suppresses EMT by constraining EGFR expression and Src activation; IL-17RA in macrophages is required for Syk activation upon dectin-1 engagement with fungi, and for IL-18 release and CD8+ T cell anti-tumor immunity; these represent two distinct tumor-suppressive IL-17RA mechanisms in colorectal cancer. Cell-type-specific conditional KO (IEC and macrophage), tumor models, Syk activation assay, immune cell profiling Immunity High 40023157
2024 TCF4 negatively regulates IL-17C; IL-17C stimulation of keratinocytes decreases TCF4 and increases NFKBIZ and ZC3H12A in an IL-17RA/IL-17RE-dependent manner, creating an autocrine inflammatory feedback loop; genetic elimination of Il17ra and Il17re reversed the loop in a murine dermatitis model. siRNA knockdown, conditional KO mouse (KC-Tie2), promoter analysis, gene expression profiling JCI insight Medium 38470486
2018 IL-17A/IL-17RA signaling promotes NSCLC cell migration and invasion via the p38 MAPK pathway; IL-17RA overexpression increased p38 phosphorylation and MMP-2/MMP-9 expression; p38 MAPK inhibitor SB203580 suppressed migration and invasion; MMP-2 and MMP-9 are downstream of IL-17RA/p38. IL-17RA overexpression, p38 MAPK inhibitor, wound healing/Transwell invasion assays, Western blotting Molecular and cellular biochemistry Medium 30564960
2021 Conditional deletion of IL-17RA in osteoclast precursors (LysM-Cre) increased trabecular bone mass and decreased osteoclast number in vivo; in vitro osteoclast formation was reduced, associated with lower abundance of osteoclast precursors. Conditional KO mouse (LysM-Cre), micro-CT, histomorphometry, in vitro osteoclastogenesis assay Bone Medium 34973492
2018 IL-17RA expression in mesenchymal stem cells (MSCs) is required for their immunosuppressive function; IL-17RA-/- MSCs showed reduced VCAM1, ICAM1, and PD-L1 expression, could not suppress Th17 proliferation, and failed to reduce EAE severity or generate regulatory T cells in vivo. IL-17RA KO MSC transplantation, EAE model, flow cytometry, in vitro suppression assay Frontiers in immunology Medium 29760692
2018 IL-17RA signaling in hepatocytes regulates IL-6 production by non-parenchymal cell recruitment, which in turn triggers hepatocyte proliferation; IL-17RA-/- mice showed delayed early-gene expression and delayed G1/S phase transition after partial hepatectomy. IL-17RA KO mouse, partial hepatectomy model, gene expression analysis, cell cycle analysis Cell cycle Medium 30395772
2011 IL-17RA PLAD (pre-ligand assembly domain) mediates receptor-chain associations essential for signaling; lentiviral IL-17RA PLAD-Ig expression in spontaneously hypertensive rats reduced collagen deposition, MMP-2/9 expression, and TIMP-1/2 levels, improving diastolic cardiac function. Lentiviral PLAD-Ig overexpression in vivo, echocardiography, immunoblotting for ECM proteins Experimental and molecular pathology Low 21530504
2019 IL-17B uses IL-17RA and IL-17RB receptor subunits to induce type 2 cytokine secretion from human innate type 2 lymphocytes, NKT, and CD4+CRTH2+ Th2 cells; this activity was dependent on both IL-17RA and IL-17RB. Receptor blocking antibodies, primary human lymphocyte functional assays, cytokine measurement Journal of immunology Medium 30770417
2019 IL-17C signals through the IL-17RA/IL-17RE receptor heterodimer in oral epithelial cells to stimulate production of TNF-α; IL-17C mRNA was expressed in cultured human oral keratinocytes that also expressed IL-17RA and IL-17RE; neutralizing IL-17C or IL-17R antibodies attenuated these responses. qRT-PCR, IL-17C stimulation assay, neutralizing antibody blockade, immunohistochemistry Journal of oral pathology & medicine Low 23834281
2012 The IL-17A/IL-17RA axis promotes aortic arch inflammation during atherosclerosis by inducing TNFα and CXCL2 and accelerating neutrophil/monocyte recruitment; IL-17RA supports monocyte adherence to explanted aortas; adoptively transferred monocytes and neutrophils showed impaired homing to IL-17RA-deficient aortas. Il17ra-/- Apoe-/- mouse model, flow cytometry, ex vivo adhesion assay, short-term homing experiments with adoptive transfer Circulation research High 22302786
2012 IL-17RA signaling is required for CXCL1/CXCL2-dependent neutrophil recruitment during T. cruzi infection; recruited neutrophils secrete IL-10 and suppress T cell proliferation and IFN-γ production in an IL-10-dependent manner; adoptive transfer of WT neutrophils restored this suppressive phenotype and improved survival in IL-17RA KO mice. IL-17RA KO mouse, neutrophil depletion (anti-Ly6G), adoptive transfer, in vitro suppression assay PLoS pathogens High 22577359

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Brodalumab, an anti-IL17RA monoclonal antibody, in psoriatic arthritis. The New England journal of medicine 308 24918373
2009 Critical role of IL-17RA in immunopathology of influenza infection. Journal of immunology (Baltimore, Md. : 1950) 298 19783685
2008 Identification of functional roles for both IL-17RB and IL-17RA in mediating IL-25-induced activities. Journal of immunology (Baltimore, Md. : 1950) 279 18768888
2008 The human IL-17F/IL-17A heterodimeric cytokine signals through the IL-17RA/IL-17RC receptor complex. Journal of immunology (Baltimore, Md. : 1950) 246 18684971
2021 Exosomes derived from human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis by miR-192-5p/IL-17RA/Smad axis. Stem cell research & therapy 217 33789737
2011 IL-17RA is required for CCL2 expression, macrophage recruitment, and emphysema in response to cigarette smoke. PloS one 186 21647421
2019 Profibrotic effect of IL-17A and elevated IL-17RA in idiopathic pulmonary fibrosis and rheumatoid arthritis-associated lung disease support a direct role for IL-17A/IL-17RA in human fibrotic interstitial lung disease. American journal of physiology. Lung cellular and molecular physiology 161 30604628
2012 The IL-17A/IL-17RA axis plays a proatherogenic role via the regulation of aortic myeloid cell recruitment. Circulation research 143 22302786
2016 Genetic, immunological, and clinical features of patients with bacterial and fungal infections due to inherited IL-17RA deficiency. Proceedings of the National Academy of Sciences of the United States of America 138 27930337
2009 Attenuated atherosclerosis upon IL-17R signaling disruption in LDLr deficient mice. Biochemical and biophysical research communications 129 19660432
2008 IL-17RA and IL-17RC receptors are essential for IL-17A-induced ELR+ CXC chemokine expression in synoviocytes and are overexpressed in rheumatoid blood. Journal of immunology (Baltimore, Md. : 1950) 111 18097068
2012 IL-17RA signaling reduces inflammation and mortality during Trypanosoma cruzi infection by recruiting suppressive IL-10-producing neutrophils. PLoS pathogens 110 22577359
2013 IL-17A and Th17 cells in lung inflammation: an update on the role of Th17 cell differentiation and IL-17R signaling in host defense against infection. Clinical & developmental immunology 86 23956759
2024 Gingerenone A Attenuates Ulcerative Colitis via Targeting IL-17RA to Inhibit Inflammation and Restore Intestinal Barrier Function. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 85 38639442
2013 IL-17RA is essential for optimal localization of follicular Th cells in the germinal center light zone to promote autoantibody-producing B cells. Journal of immunology (Baltimore, Md. : 1950) 75 23858031
2022 IL-17RA-signaling in Lgr5+ intestinal stem cells induces expression of transcription factor ATOH1 to promote secretory cell lineage commitment. Immunity 73 35081371
2010 IL-17A- versus IL-17F-induced intracellular signal transduction pathways and modulation by IL-17RA and IL-17RC RNA interference in rheumatoid synoviocytes. Annals of the rheumatic diseases 69 21109515
2020 Structural Analysis Reveals that the Cytokine IL-17F Forms a Homodimeric Complex with Receptor IL-17RC to Drive IL-17RA-Independent Signaling. Immunity 65 32187518
2021 Vaccine-driven lung TRM cells provide immunity against Klebsiella via fibroblast IL-17R signaling. Science immunology 63 34516780
2016 IL-17RA in Non-Hematopoietic Cells Controls CXCL-1 and 5 Critical to Recruit Neutrophils to the Lung of Mycobacteria-Infected Mice during the Adaptive Immune Response. PloS one 60 26871571
2018 IL-17A/IL-17RA promotes invasion and activates MMP-2 and MMP-9 expression via p38 MAPK signaling pathway in non-small cell lung cancer. Molecular and cellular biochemistry 58 30564960
2012 Association between IL17A/IL17RA Gene Polymorphisms and Susceptibility to Alopecia Areata in the Korean Population. Annals of dermatology 58 22363157
2010 IL-17A suppresses the expression of bone resorption-related proteinases and osteoclast differentiation via IL-17RA or IL-17RC receptors in RAW264.7 cells. Biochimie 58 20045440
2017 The flavonoid cyanidin blocks binding of the cytokine interleukin-17A to the IL-17RA subunit to alleviate inflammation in vivo. Science signaling 57 28223414
2017 Interleukin 17 regulates SHP-2 and IL-17RA/STAT-3 dependent Cyr61, IL-23 and GM-CSF expression and RANKL mediated osteoclastogenesis by fibroblast-like synoviocytes in rheumatoid arthritis. Molecular immunology 57 28898718
2011 IL-17RA aptamer-mediated repression of IL-6 inhibits synovium inflammation in a murine model of osteoarthritis. Osteoarthritis and cartilage 57 21310253
2015 IL-17RA Signaling in Airway Inflammation and Bronchial Hyperreactivity in Allergic Asthma. American journal of respiratory cell and molecular biology 55 25919006
2007 IL-17A versus IL-17F induced intracellular signal transduction pathways and modulation by IL-17RA and IL-17RC RNA interference in AGS gastric adenocarcinoma cells. Cytokine 54 17644350
2021 Efficacy and safety of brodalumab, an anti-IL17RA monoclonal antibody, in patients with axial spondyloarthritis: 16-week results from a randomised, placebo-controlled, phase 3 trial. Annals of the rheumatic diseases 53 33827787
2019 IL-17A promotes fatty acid uptake through the IL-17A/IL-17RA/p-STAT3/FABP4 axis to fuel ovarian cancer growth in an adipocyte-rich microenvironment. Cancer immunology, immunotherapy : CII 53 31802182
2005 IL-17R activation of human airway smooth muscle cells induces CXCL-8 production via a transcriptional-dependent mechanism. Clinical immunology (Orlando, Fla.) 53 15893694
2023 Candida albicans Promotes Oral Cancer via IL-17A/IL-17RA-Macrophage Axis. mBio 50 37067414
2015 Association between single nucleotide polymorphisms IL17RA rs4819554 and IL17E rs79877597 and Psoriasis in a Spanish cohort. Journal of dermatological science 49 26347322
2010 SEF/IL-17R (SEFIR) is not enough: an extended SEFIR domain is required for il-17RA-mediated signal transduction. The Journal of biological chemistry 49 20729198
2023 IL-17A functions and the therapeutic use of IL-17A and IL-17RA targeted antibodies for cancer treatment. International immunopharmacology 48 37579542
2016 Inhibiting complex IL-17A and IL-17RA interactions with a linear peptide. Scientific reports 48 27184415
2011 A CC' loop decoy peptide blocks the interaction between Act1 and IL-17RA to attenuate IL-17- and IL-25-induced inflammation. Science signaling 46 22045852
2010 IL-17R activation of human periodontal ligament fibroblasts induces IL-23 p19 production: Differential involvement of NF-κB versus JNK/AP-1 pathways. Molecular immunology 38 21145111
2022 FTO promotes liver inflammation by suppressing m6A mRNA methylation of IL-17RA. Frontiers in oncology 37 36172147
2020 IL-17A is involved in diabetic inflammatory pathogenesis by its receptor IL-17RA. Experimental biology and medicine (Maywood, N.J.) 36 32903039
2018 IL-17RA-Signaling Modulates CD8+ T Cell Survival and Exhaustion During Trypanosoma cruzi Infection. Frontiers in immunology 36 30364284
2016 The IL-17A/IL-17RA axis in pulmonary defence and immunopathology. Cytokine & growth factor reviews 36 27033174
2016 IL17RA gene variants and anti-TNF response among psoriasis patients. The pharmacogenomics journal 36 27670766
2021 From Messengers to Receptors in Psoriasis: The Role of IL-17RA in Disease and Treatment. International journal of molecular sciences 34 34201664
2012 IL-17A/IL-17RA interaction promoted metastasis of osteosarcoma cells. Cancer biology & therapy 34 23192273
2011 IL-17RA signaling amplifies antibody-induced arthritis. PloS one 33 22028860
2012 Interleukin-25 promotes basic fibroblast growth factor expression by human endothelial cells through interaction with IL-17RB, but not IL-17RA. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 32 23106660
2017 Monoclonal Antibodies Targeting the IL-17/IL-17RA Axis: An Opportunity to Improve the Efficiency of Anti-VEGF Therapy in Fighting Metastatic Colorectal Cancer? Clinical colorectal cancer 31 29153431
2013 IL-17C and its receptor IL-17RA/IL-17RE identify human oral epithelial cell as an inflammatory cell in recurrent aphthous ulcer. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 31 23834281
2022 Cardiomyocyte IL-1R2 protects heart from ischemia/reperfusion injury by attenuating IL-17RA-mediated cardiomyocyte apoptosis. Cell death & disease 30 35087030
2016 Preferential expression of functional IL-17R in glioma stem cells: potential role in self-renewal. Oncotarget 29 26755664
2022 IL-17-induced dimerization of IL-17RA drives the formation of the IL-17 signalosome to potentiate signaling. Cell reports 27 36260993
2019 Secukinumab attenuates reactive astrogliosis via IL-17RA/(C/EBPβ)/SIRT1 pathway in a rat model of germinal matrix hemorrhage. CNS neuroscience & therapeutics 27 31020769
2018 IL17/IL17RA as a Novel Signaling Axis Driving Mesenchymal Stem Cell Therapeutic Function in Experimental Autoimmune Encephalomyelitis. Frontiers in immunology 27 29760692
2014 Toll-like receptor signaling directly increases functional IL-17RA expression in neuroglial cells. Clinical immunology (Orlando, Fla.) 27 25076485
2022 Small molecule modulators of IL-17A/IL-17RA: a patent review (2013-2021). Expert opinion on therapeutic patents 26 36350977
2019 Cutting Edge: IL-17B Uses IL-17RA and IL-17RB to Induce Type 2 Inflammation from Human Lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 26 30770417
2018 RKIP mediates autoimmune inflammation by positively regulating IL-17R signaling. EMBO reports 26 29674348
2012 Association of single nucleotide polymorphisms on Interleukin 17 receptor A (IL17RA) gene with aspirin hypersensitivity in asthmatics. Human immunology 25 23220496
2019 Intestinal IL-17R Signaling Constrains IL-18-Driven Liver Inflammation by the Regulation of Microbiome-Derived Products. Cell reports 24 31747600
2019 Oxidative stress-induced KLF4 activates inflammatory response through IL17RA and its downstream targets in retinal pigment epithelial cells. Free radical biology & medicine 24 31881336
2018 Cigarette Smoke Extract Enhances IL-17A-Induced IL-8 Production via Up-Regulation of IL-17R in Human Bronchial Epithelial Cells. Molecules and cells 24 29463070
2017 Interleukin-17 receptor A (IL-17RA) as a central regulator of the protective immune response against Giardia. Scientific reports 24 28819174
2016 Common variants in IL-17A/IL-17RA axis contribute to predisposition to and progression of congestive heart failure. Medicine 24 27399111
2011 Lentivirus mediated IL-17R blockade improves diastolic cardiac function in spontaneously hypertensive rats. Experimental and molecular pathology 24 21530504
2019 Ferulic acid altered IL-17A/IL-17RA interaction and protected against imiquimod-induced psoriasis-like skin injury in mice. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 23 31054998
2018 Locally Targeting the IL-17/IL-17RA Axis Reduced Tumor Growth in a Murine B16F10 Melanoma Model. Human gene therapy 23 30079767
2017 Cordycepin and a preparation from Cordyceps militaris inhibit malignant transformation and proliferation by decreasing EGFR and IL-17RA signaling in a murine oral cancer model. Oncotarget 23 29212184
2017 Increased IL-17RA and IL-17RC in End-Stage COPD and the Contribution to Mast Cell Secretion of FGF-2 and VEGF. Respiratory research 21 28298222
2015 Brodalumab -an IL-17RA monoclonal antibody for psoriasis and psoriatic arthritis. Expert opinion on biological therapy 21 25985813
2021 An Analysis of IL-10, IL-17A, IL-17RA, IL-23A and IL-23R Expression and Their Correlation with Clinical Course in Patients with Psoriasis. Journal of clinical medicine 20 34945130
2017 Upregulation of miR-215 exerts neuroprotection effects against ischemic injury via negative regulation of Act1/IL-17RA signaling. Neuroscience letters 20 29080697
2019 Characteristic Pattern of IL-17RA, IL-17RB, and IL-17RC in Monocytes/Macrophages and Mast Cells From Patients With Bullous Pemphigoid. Frontiers in immunology 19 31572359
2016 A Single Nucleotide Polymorphism in the Il17ra Promoter Is Associated with Functional Severity of Ankylosing Spondylitis. PloS one 19 27415816
2015 Association between the IL17RA rs4819554 polymorphism and reduced renal filtration rate in the Spanish RENASTUR cohort. Human immunology 19 25636567
2013 Identification of a soluble isoform of human IL-17RA generated by alternative splicing. Cytokine 19 24084331
2017 Ultraviolet B Inhibits IL-17A/TNF-α-Stimulated Activation of Human Dermal Fibroblasts by Decreasing the Expression of IL-17RA and IL-17RC on Fibroblasts. Frontiers in immunology 18 28217129
2024 IL-17A/IL-17RA interaction blockade sensitizes synovial macrophages to efferocytosis and PD-L1 signaling via rewiring STAT-3/ADAM17/MERTK axis in rheumatoid arthritis animal model. International immunopharmacology 17 38810305
2017 Artificial Macrocycles as IL-17A/IL-17RA Antagonists. MedChemComm 17 29750108
2021 Deletion of IL-17ra in osteoclast precursors increases bone mass by decreasing osteoclast precursor abundance. Bone 16 34973492
2024 Suppression of TCF4 promotes a ZC3H12A-mediated self-sustaining inflammatory feedback cycle involving IL-17RA/IL-17RE epidermal signaling. JCI insight 15 38470486
2019 IL-17A Recruits Rab35 to IL-17R to Mediate PKCα-Dependent Stress Fiber Formation and Airway Smooth Muscle Contractility. Journal of immunology (Baltimore, Md. : 1950) 15 30683702
2014 IL-17 and IL-17R: an auspicious therapeutic target for psoriatic disease. Actas dermo-sifiliograficas 15 25398489
2012 Genetic ablation of PI3Kγ results in defective IL-17RA signalling in T lymphocytes and increased IL-17 levels. European journal of immunology 15 22930133
2025 IL-17RA signaling provides dual tumor-suppressor function during late-stage colorectal carcinogenesis. Immunity 14 40023157
2019 A potential association between psoriasin to rs4819554 of IL-17RA gene polymorphism in psoriasis Egyptian patients. Archives of dermatological research 14 31745628
2015 The IL17F and IL17RA Genetic Variants Increase Risk of Cerebral Malaria in Two African Populations. Infection and immunity 14 26667835
2021 Intestinal IL-17R Signaling Controls Secretory IgA and Oxidase Balance in Citrobacter rodentium Infection. Journal of immunology (Baltimore, Md. : 1950) 13 33431657
2021 Extracorporeal Shockwave Therapy Modulates the Expressions of Proinflammatory Cytokines IL33 and IL17A, and Their Receptors ST2 and IL17RA, within the Articular Cartilage in Early Avascular Necrosis of the Femoral Head in a Rat Model. Mediators of inflammation 13 34305456
2024 Inhibition of IL-25/IL-17RA improves immune-related adverse events of checkpoint inhibitors and reveals antitumor activity. Journal for immunotherapy of cancer 12 38519059
2022 Serum IL-17A concentration and a IL17RA single nucleotide polymorphism contribute to the risk of autoimmune type 1 diabetes. Diabetes/metabolism research and reviews 12 35583128
2022 Secukinumab alleviates cognitive impairment by attenuating oxidative stress and neuronal apoptosis via the IL-17RA/AKT/ERK1/2 pathway in a rat model of sepsis. Experimental neurology 12 36336029
2019 IL-17R deletion predicts high-grade colorectal cancer and poor clinical outcomes. International journal of cancer 12 30628053
2019 IL-17A neutralizing antibody attenuates eosinophilic meningitis caused by Angiostrongylus cantonensis by involving IL-17RA/Traf6/NF-κB signaling. Experimental cell research 12 31415761
2021 Association between IL-17A, IL-17F and IL-17RA gene polymorphisms and susceptibility to psoriasis and psoriatic arthritis: a meta-analysis. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 11 34705056
2023 Immunogenic Cell Death Associated Molecular Patterns and the Dual Role of IL17RA in Interstitial Cystitis/Bladder Pain Syndrome. Biomolecules 10 36979355
2018 Role of IL-17RA in the proliferative priming of hepatocytes in liver regeneration. Cell cycle (Georgetown, Tex.) 10 30395772
2015 IL-17RA in intestinal inflammation: structure, signaling, function, and clinical application. Inflammatory bowel diseases 10 25272188
2014 The effect of proinflammatory cytokines on IL-17RA expression in NSCLC. Medical oncology (Northwood, London, England) 10 25112467
2022 IL-17RA receptor signaling contributes to lung inflammation and parasite burden during Toxocara canis infection in mice. Frontiers in immunology 9 35844540

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