Affinage

IL17RA

Interleukin-17 receptor A · UniProt Q96F46

Length
866 aa
Mass
96.1 kDa
Annotated
2026-04-28
100 papers in source corpus 39 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL-17RA is the obligate shared receptor subunit for multiple IL-17 family cytokines, forming heteromeric signaling complexes with IL-17RC (for IL-17A, IL-17F, and IL-17A/F) and IL-17RB (for IL-17E/IL-25 and IL-17B) that assemble into hexameric signalosomes upon ligand-induced IL-17RA dimerization (PMID:36260993, PMID:18768888, PMID:18684971, PMID:30770417). Upon cytokine engagement, IL-17RA recruits the adaptor Act1 via SEFIR-domain CC' loop interactions, leading to TRAF6 ubiquitination and activation of NF-κB and MAPK (ERK, p38, JNK) cascades that drive chemokine and cytokine production in structural cells including epithelial cells, fibroblasts, and airway smooth muscle (PMID:22045852, PMID:20729198, PMID:21109515, PMID:15893694). Cell-type-specific IL-17RA signaling governs neutrophil recruitment, intestinal secretory cell differentiation via ATOH1 induction in stem cells, mucosal barrier integrity through IgA and hydrogen peroxide regulation, airway smooth muscle contraction via a Rab35/PKCα/stress fiber axis, osteoclast precursor abundance, and macrophage efferocytosis through ADAM17-mediated MERTK shedding (PMID:35081371, PMID:30683702, PMID:33431657, PMID:34973492, PMID:38810305, PMID:26871571). Autosomal recessive loss-of-function mutations in IL-17RA abolish responses to IL-17A/F and IL-17E, causing chronic mucocutaneous candidiasis and staphylococcal disease (PMID:27930337).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2005 High

    Establishing that IL-17RA is expressed on non-immune structural cells and directly drives chemokine transcription resolved how IL-17 signals provoke neutrophilic inflammation at tissue sites.

    Evidence IL-17RA expression confirmed on human airway smooth muscle cells by RT-PCR and immunostaining; CXCL-8 promoter reporter assays with NF-κB/AP-1 site mutations

    PMID:15893694

    Open questions at the time
    • Downstream adaptor proteins not yet identified
    • Whether other IL-17R subunits are required was unknown
  2. 2008 High

    Identifying IL-17RA as a shared subunit required for both IL-17A/F (with IL-17RC) and IL-25 (with IL-17RB) signaling established IL-17RA as the central hub of the IL-17 receptor family.

    Evidence Reciprocal KO mice (IL-17RA, IL-17RB), siRNA knockdown of IL-17RA/RC in synoviocytes and bronchial epithelial cells, SPR binding affinity measurements

    PMID:18097068 PMID:18684971 PMID:18768888

    Open questions at the time
    • Structural basis for how one receptor subunit participates in distinct heteromeric complexes was unknown
    • Intracellular signaling domain architecture not yet mapped
  3. 2009 High

    Demonstrating that IL-17RA drives neutrophil recruitment and oxidative damage but is dispensable for viral clearance delineated the immunopathological versus protective roles of IL-17RA in infection.

    Evidence IL-17RA−/− mice in influenza infection model with dissection of neutrophil, MPO, oxidized phospholipid, and CD8+ T cell responses

    PMID:19783685

    Open questions at the time
    • Cell-type-specific contributions of IL-17RA (hematopoietic vs structural) not yet resolved in this model
  4. 2010 High

    Mapping the IL-17RA intracellular signaling requirements revealed that Act1 recruitment via the SEFIR domain is necessary but insufficient, and that TRAF6 ubiquitination is the critical downstream checkpoint for NF-κB/MAPK activation.

    Evidence Structure-function mutagenesis of IL-17RA C-terminal domain; siRNA of IL-17RA/RC with NF-κB, AP-1, ERK, p38, JNK readouts in synoviocytes

    PMID:20729198 PMID:21109515

    Open questions at the time
    • Precise structural interface between Act1 SEFIR and IL-17RA SEFIR not yet resolved
    • Additional adaptor proteins potentially involved were unknown
  5. 2011 High

    Pinpointing the CC' loop of the Act1 SEFIR domain as the critical interaction surface with IL-17RA provided a targetable interface for therapeutic disruption of IL-17 signaling.

    Evidence SPR showing direct CC' loop peptide binding to IL-17RA; cell-permeable decoy peptide inhibited IL-17 and IL-25 signaling in vitro and pulmonary inflammation in vivo

    PMID:22045852

    Open questions at the time
    • Atomic-resolution structure of the Act1-IL-17RA SEFIR complex not determined
    • Whether the CC' loop peptide affects all IL-17RA heteromeric complexes equally was not tested
  6. 2011 Medium

    Identifying the pre-ligand assembly domain (PLAD) of IL-17RA as mediating receptor-chain associations before ligand binding revealed a pre-assembly mechanism for IL-17 signaling competence.

    Evidence Lentiviral delivery of IL-17RA PLAD-Ig fusion in spontaneously hypertensive rats reduced collagen/MMP production and improved cardiac function

    PMID:21530504

    Open questions at the time
    • PLAD-mediated assembly not confirmed by structural methods
    • Single disease model; generalizability to other IL-17RA-dependent contexts untested
    • No independent replication
  7. 2012 High

    Demonstrating that IL-17RA signaling in fibroblasts and vascular cells drives inflammatory mediator production in arthritis and atherosclerosis models extended the receptor's role from antimicrobial defense to chronic inflammatory disease pathogenesis.

    Evidence IL-17RA−/− mice in K/BxN serum-transfer arthritis and ApoE−/− atherosclerosis models with defined chemokine, MMP, and leukocyte recruitment readouts

    PMID:22028860 PMID:22302786

    Open questions at the time
    • Cell-type-specific conditional deletions not yet performed in these models
    • Relative contribution of IL-17A vs IL-17F to each disease model not dissected
  8. 2013 High

    Revealing that IL-17RA on TFH cells governs germinal center positioning via RGS16 upregulation extended IL-17RA function beyond structural cells to adaptive immune cell guidance.

    Evidence BXD2-Il17ra−/− mice, confocal microscopy of GC light zone localization, BXD2-Rgs16−/− mice phenocopy

    PMID:23858031

    Open questions at the time
    • Whether this TFH-intrinsic IL-17RA role operates outside the BXD2 autoimmune context is unknown
    • Direct signaling cascade from IL-17RA to RGS16 transcription not mapped
  9. 2016 High

    Bone marrow chimera and conditional deletion experiments established that non-hematopoietic (structural) cells are the primary responders through IL-17RA for neutrophil-recruiting chemokine production during pulmonary infection, and that IL-17RA in osteoclast precursors promotes osteoclastogenesis.

    Evidence IL-17RA−/− bone marrow chimeras in mycobacterial infection; LysM-Cre conditional IL-17RA KO with microCT and histomorphometry

    PMID:26871571 PMID:34973492

    Open questions at the time
    • Identity of specific structural cell subtype (epithelial vs fibroblast vs endothelial) driving chemokine production in infection not resolved
    • Osteoclast precursor study from single lab
  10. 2016 High

    Characterization of 21 patients with autosomal recessive IL-17RA deficiency definitively established IL-17RA as essential for human mucocutaneous immunity against Candida and Staphylococcus, abolishing responses to IL-17A/F and IL-17E.

    Evidence Primary fibroblast and leukocyte functional assays from patients with 12 different loss-of-function IL-17RA alleles

    PMID:27930337

    Open questions at the time
    • Genotype-phenotype correlations for partial vs complete loss-of-function alleles not fully delineated
    • Whether residual signaling through other IL-17R complexes compensates in mild alleles was not tested
  11. 2018 High

    Identification of RKIP as a scaffolding partner that bridges IL-17RA and Act1 revealed an additional layer of regulation in IL-17R signalosome assembly, with functional consequences for Th17-driven autoimmunity.

    Evidence Co-IP of RKIP with IL-17RA and Act1; RKIP−/− mice selectively resistant to Th17- but not Th1-driven EAE

    PMID:29674348

    Open questions at the time
    • Structural basis for RKIP bridging IL-17RA and Act1 unknown
    • Whether RKIP modulates all IL-17RA heteromeric complexes or only IL-17RA/RC not tested
  12. 2019 High

    Mapping the IL-17RA/Act1–Rab35/DennD1C–PKCα–fascin axis in airway smooth muscle established a non-canonical IL-17RA effector pathway directly linking cytokine signaling to cytoskeletal remodeling and contractile function.

    Evidence Cell-type-specific IL-17R/Act1 deletion in airway smooth muscle; Co-IP of Rab35/DennD1C with IL-17R/Act1 complex; Rab35 KD, PKCα inhibitor, stress fiber imaging

    PMID:30683702

    Open questions at the time
    • Whether this cytoskeletal pathway operates in non-smooth-muscle cell types is unknown
    • Direct kinase-substrate relationship between PKCα and fascin at Ser39 not demonstrated in this IL-17 context by in vitro kinase assay
  13. 2019 High

    Conditional deletion of IL-17RA in intestinal epithelium revealed its role in maintaining microbiome homeostasis and preventing bacterial product translocation, and separately showed fibroblast-specific IL-17RA/STAT3 is required for vaccine-elicited pulmonary immunity.

    Evidence Intestinal epithelium-specific and fibroblast-specific IL-17RA conditional KO mice in hepatitis, C. rodentium infection, and Klebsiella vaccine models

    PMID:31747600 PMID:33431657 PMID:34516780

    Open questions at the time
    • How IL-17RA regulates hydrogen peroxide production mechanistically is not resolved
    • Whether fibroblast IL-17RA/STAT3 axis operates in non-pulmonary mucosal tissues unknown
  14. 2020 High

    Crystal structures of IL-17RC–IL-17F and IL-17RA–IL-17RC–IL-17A complexes revealed the hexameric signalosome architecture and showed that IL-17RA dimerization is functionally required for downstream gene expression.

    Evidence X-ray crystallography of extracellular domains; IL-17RA dimerization-defective mutant with keratinocyte gene expression assays

    PMID:32187518 PMID:36260993

    Open questions at the time
    • Full-length receptor complex structure including intracellular domains not determined
    • How hexameric assembly propagates signal across the membrane to recruit Act1 is structurally unresolved
  15. 2022 High

    Demonstrating that IL-17RA in Lgr5+ intestinal stem cells induces ATOH1 to commit secretory cell lineages revealed a regenerative, non-inflammatory function of IL-17RA in tissue homeostasis.

    Evidence Multiple conditional deletions (Lgr5-Cre, ATOH1-Cre), intestinal injury models, human organoid IL-17A stimulation

    PMID:35081371

    Open questions at the time
    • Signaling intermediates between IL-17RA and ATOH1 transcriptional induction not identified
    • Whether this pathway is active under homeostatic conditions without injury is unclear
  16. 2024 Medium

    Identification of IL-17RA-dependent ADAM17-mediated MERTK shedding as the mechanism by which IL-17A impairs macrophage efferocytosis provided a mechanistic link between IL-17 signaling and failed inflammation resolution in arthritis.

    Evidence IL-17RA silencing and cyanidin treatment restored efferocytosis; ADAM17 KD phenocopied; adjuvant-induced arthritis model

    PMID:38810305

    Open questions at the time
    • Single lab; independent replication needed
    • Whether MERTK shedding by IL-17RA/ADAM17 operates in tissue macrophages beyond the synovium is untested
  17. 2025 High

    Dual cell-type-specific roles of IL-17RA were delineated in colorectal cancer: suppression of EMT via EGFR/Src restraint in epithelial cells, and enabling Syk-dependent IL-18 release from macrophages for anti-tumor CD8+ T cell immunity.

    Evidence Conditional IL-17RA deletion in IECs and macrophages; CRC mouse model; EGFR/Src and dectin-1/Syk pathway analysis

    PMID:40023157

    Open questions at the time
    • How IL-17RA restrains EGFR/Src mechanistically is not fully resolved
    • Relevance to human CRC not yet demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length structural model of the IL-17RA signalosome spanning extracellular hexamer through transmembrane to intracellular SEFIR–Act1–TRAF6 assembly remains undetermined, and cell-type-specific transcriptional programs downstream of the common IL-17RA signal are incompletely mapped.
  • No full-length receptor complex structure exists
  • Mechanisms selecting between NF-κB, MAPK, STAT3, and non-canonical (Rab35) pathways in different cell types are unknown
  • How IL-17RA expression is regulated at the post-transcriptional level (beyond FTO/m6A) is poorly understood

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 5 R-HSA-1266738 Developmental Biology 1
Partners
DENND1CIL17RBIL17RCPEBP1RAB35TRAF1IP2TRAF6
Complex memberships
IL-17RA/Act1/TRAF6IL-17RA/IL-17RBIL-17RA/IL-17RC

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 IL-25 (IL-17E) signaling requires both IL-17RB and IL-17RA subunits to form a functional heteromeric receptor complex; knockout of either subunit or antibody blockade of either receptor abolishes IL-25-induced IL-5/IL-13 production and pulmonary inflammation in vivo. Knockout mice (IL-17RB KO and IL-17RA KO), antagonistic monoclonal antibodies, in vitro splenocyte assays, intranasal IL-25 challenge model Journal of immunology High 18768888
2008 The IL-17F/IL-17A heterodimeric cytokine signals through the IL-17RA/IL-17RC receptor complex; IL-17RA binds IL-17A with higher affinity than IL-17F or the heterodimer (measured by surface plasmon resonance), while IL-17RC binds all three cytokines with comparable affinity; soluble IL-17RA preferentially neutralizes IL-17A activity. siRNA knockdown of IL-17RA and IL-17RC, surface plasmon resonance (binding affinity), soluble receptor neutralization assays, bronchial epithelial cell cytokine secretion assays Journal of immunology High 18684971
2008 Both IL-17RA and IL-17RC are required for IL-17A-induced ELR+ CXC chemokine (IL-6, IL-8, CCL-20) expression in synoviocytes; siRNA silencing of either receptor abrogates IL-17A-mediated signaling, and combined inhibition is required when TNF-α is also present. siRNA knockdown of IL-17RA and IL-17RC in rheumatoid arthritis synoviocytes, ELISA, microarray gene expression analysis Journal of immunology High 18097068
2010 IL-17RA-mediated signaling requires an extended C-terminal domain beyond the previously identified SEFIR motif; Act1 recruitment to IL-17RA is necessary but not sufficient for downstream signaling, whereas TRAF6 ubiquitination correlates tightly with functional receptor activity. IL-17RA signals synergistically with lymphotoxin-α3 using the same signaling motifs. Structure-function mutagenesis of IL-17RA C-terminal domain, Act1 recruitment assays, TRAF6 ubiquitination assays, cell-based signaling readouts The Journal of biological chemistry High 20729198
2011 The CC' loop of the SEFIR domain of Act1 directly mediates interaction with IL-17RA; a cell-permeable decoy peptide based on the CC' loop sequence inhibits IL-17- and IL-25-mediated signaling in vitro and pulmonary inflammation in vivo. Deletion of the BB' loop (unlike in TIR domains) does not affect Act1-IL-17RA interaction. Domain deletion mutagenesis, surface plasmon resonance (direct binding of CC' loop peptide to IL-17RA), cell-permeable peptide in vitro and in vivo inhibition, pulmonary inflammation mouse model Science signaling High 22045852
2011 IL-17RA signaling is required for CCL2 and MMP12 expression and macrophage recruitment in the lung in response to cigarette smoke; IL-17RA-deficient mice fail to develop emphysema after 6 months of cigarette smoke exposure. IL-17RA knockout mice, cigarette smoke exposure model, qPCR for CCL2/MMP12, histological assessment of emphysema PloS one High 21647421
2012 IL-17RA signaling amplifies inflammatory arthritis by directly activating synovial fibroblasts to produce multiple pro-inflammatory mediators (CXCL1, CXCL2, CXCL5, IL-1β, IL-6, RANKL, MMP2, MMP3, MMP13); IL-17RA-deficient mice show reduced cartilage and bone erosions in the K/BxN serum-transfer arthritis model. IL-17RA knockout mice in K/BxN serum-transfer arthritis model, qPCR for cytokines/chemokines, in vitro IL-17A stimulation of synovial fibroblasts, histological bone/cartilage assessment PloS one High 22028860
2012 IL-17RA signaling in the aortic vasculature promotes atherosclerotic plaque formation by inducing aortic chemokines (TNFα, CXCL2) and supporting monocyte/neutrophil adherence and recruitment to the aortic arch; IL-17RA-deficient Apoe-/- mice show reduced aortic arch atherosclerosis. IL-17RA-/- x Apoe-/- double-knockout mice, Western diet feeding, flow cytometry, ex vivo monocyte adhesion assays, short-term adoptive transfer homing experiments Circulation research High 22302786
2013 IL-17RA expressed on follicular T helper (TFH) cells is required for their localization to the germinal center light zone and interaction with B cells; IL-17 upregulates RGS16 in TFH cells to promote TFH-B cell conjugate formation, leading to autoantibody-producing B cell generation in BXD2 mice. BXD2-Il17ra-/- mice, conditional IL-17R:Fc blockade, confocal microscopy of GC light zone localization, in vitro B cell response assays, RGS16 expression analysis, BXD2-Rgs16-/- mice Journal of immunology High 23858031
2016 Inherited autosomal recessive IL-17RA deficiency in humans abolishes cellular responses to IL-17A, IL-17F homodimers, IL-17A/F heterodimers (in fibroblasts), and IL-17E/IL-25 (in leukocytes), establishing IL-17RA as essential for mucocutaneous immunity to Candida and Staphylococcus. Primary fibroblast and leukocyte functional assays from 21 patients with defined IL-17RA loss-of-function mutations; surface expression of 12 different IL-17RA alleles characterized Proceedings of the National Academy of Sciences High 27930337
2017 Cyanidin specifically binds to an IL-17A-binding site on IL-17RA, blocking the IL-17A/IL-17RA protein-protein interaction; this inhibits IL-17A-induced skin hyperplasia and TH17-mediated airway inflammation in vivo. Structure-based virtual screening, molecular binding assays, murine skin hyperplasia model, murine asthma models, selectivity testing against TH1/TH2-mediated inflammation Science signaling High 28223414
2018 RKIP (Raf-1 kinase inhibitor protein) directly interacts with both IL-17RA and Act1 to promote formation of the IL-17R-Act1 signaling complex, resulting in enhanced MAPK and NF-κB activation and downstream inflammatory cytokine production; RKIP deficiency ameliorates experimental autoimmune encephalomyelitis (EAE) by impeding Th17- but not Th1-mediated responses. Co-immunoprecipitation of RKIP with IL-17RA and Act1, adoptive T-cell transfer (Th17 vs Th1), RKIP-deficient mice in EAE model, cytokine/chemokine production assays EMBO reports High 29674348
2019 IL-17A recruits Rab35 (and its GEF DennD1C) to the IL-17R/Act1 complex in airway smooth muscle cells, activating Rab35 to promote PKCα activation and fascin phosphorylation at Ser39, allowing F-actin/myosin stress fiber formation and enhanced airway smooth muscle contraction. Cell type-specific IL-17R/Act1 deletion, Co-IP of Rab35/DennD1C with IL-17R/Act1 complex, Rab35 knockdown, PKCα inhibitor, immunofluorescence for stress fibers, airway smooth muscle contraction assay Journal of immunology High 30683702
2020 Crystal structure of the extracellular domain of IL-17RC in complex with IL-17F reveals that IL-17RC forms a symmetrical 2:1 complex with IL-17F, competing with IL-17RA for cytokine binding; IL-17A and IL-17A/F heterodimer also form 2:1 complexes with IL-17RC, demonstrating the structural basis for potential IL-17RA-independent signaling. X-ray crystallography of IL-17RC:IL-17F complex, biophysical techniques to characterize IL-17A and IL-17A/F complexes with IL-17RC Immunity High 32187518
2022 IL-17A, IL-17F, and IL-17A/F induce IL-17RA dimerization; X-ray crystallography of the heteromeric IL-17A complex with extracellular domains of IL-17RA and IL-17RC reveals a 2:2:2 hexameric signaling assembly (signalosome); formation of this signalosome potentiates IL-17-induced IL-36γ and CXCL1 expression in human keratinocytes compared to a dimerization-defective IL-17RA variant. X-ray crystallography, biophysical binding studies, mutagenesis of IL-17RA dimerization interface, keratinocyte gene expression assays Cell reports High 36260993
2022 IL-17RA signaling in Lgr5+ intestinal stem cells induces ATOH1 transcription factor expression to promote secretory cell lineage commitment (Paneth, tuft, goblet, enteroendocrine cells); IL-17RA signaling in ATOH1+ cells is required to regenerate secretory cells following injury; IL-17A stimulation of human intestinal organoids rescues secretory cell differentiation. Multiple conditional deletion models (Lgr5-Cre, ATOH1-Cre), intestinal injury models, human intestinal organoid stimulation, lineage tracing, cell counting Immunity High 35081371
2022 FTO (fat mass and obesity-associated RNA demethylase) reduces m6A methylation of IL-17RA mRNA in liver tissue, increasing IL-17RA expression and promoting chronic hepatic inflammation; knockdown and overexpression of FTO in vitro and in vivo confirm FTO as the main modulator of IL-17RA m6A levels. MeRIP-seq on human liver tissues, FTO knockdown/overexpression in vitro and in vivo, NAFLD and chronic liver injury mouse models, comparison with METTL3, METTL14, ALKBH5 Frontiers in oncology Medium 36172147
2019 IL-17A signals through the IL-17A/IL-17RA/p-STAT3/FABP4 axis in ovarian cancer cells to promote fatty acid uptake and cancer cell proliferation in an adipocyte-rich microenvironment; this is dependent on IL-17RA but not CD36. In vitro palmitic acid uptake assays with IL-17A stimulation, IL-17RA pathway analysis, orthotopic implantation model in IL-17A-deficient mice, FABP4 and p-STAT3 expression analysis Cancer immunology, immunotherapy Medium 31802182
2010 IL-17A and IL-17F both signal through IL-17RA and IL-17RC in rheumatoid synoviocytes activating NF-κB and MAPKs; siRNA silencing of either receptor nearly completely abrogates IL-17A-mediated IL-6 expression and IL-17F+TNF-α-mediated responses; IL-17A activates ERK, p38, JNK and induces TRAF6 but not MyD88. Affymetrix microarrays, ELISA, siRNA knockdown of IL-17RA/RC, Western blotting, NF-κB and AP-1 DNA binding assays Annals of the rheumatic diseases High 21109515
2013 A soluble isoform of human IL-17RA is generated by alternative splicing (exclusion of exon 11 encoding the transmembrane region) and is secreted into cell culture media, providing a potential endogenous regulator of IL-17RA-mediated responses. RT-PCR in human tissues, Western blotting of culture media to detect soluble isoform protein Cytokine Medium 24084331
2019 IL-17RA signaling in intestinal epithelial cells regulates the microbiome and constrains bacterial product (CpG DNA) translocation to the liver; absence of intestinal epithelial IL-17RA leads to microbiome dysbiosis, increased hepatic IL-18 production, and exacerbated immune-driven hepatitis. Intestinal epithelium-specific IL-17RA-deficient mice (conditional KO), immune-driven hepatitis model, microbiome analysis, bacterial product translocation assays, IL-18 measurement Cell reports High 31747600
2019 IL-17RA signaling in non-hematopoietic lung fibroblasts (rather than hematopoietic cells) is required for vaccine-elicited TH17-mediated lung-specific immunity to Klebsiella pneumoniae, acting through STAT3 expression. Fibroblast-specific IL-17RA deletion, STAT3-deficient mice, adoptive transfer of vaccine-elicited CD4+ T cells, lung-specific immunity readouts Science immunology High 34516780
2016 IL-17RA expressed on non-hematopoietic (structural) lung cells is required for CXCL-1 and CXCL-5 production and subsequent adaptive neutrophil recruitment during Mycobacteria infection; CXCL-1/5 instillation rescues neutrophil recruitment in IL-17RA-/- mice. IL-17RA-/- mice, BCG/Mtb intranasal infection model, bone marrow chimeras to distinguish hematopoietic vs non-hematopoietic IL-17RA, CXCL-1/5 reconstitution experiment PloS one High 26871571
2019 IL-17A signals through IL-17RA to activate NF-κB-mediated fibrogenic responses in lung fibroblasts (ECM production, myofibroblast transdifferentiation, proliferation); siRNA silencing of IL-17RA attenuates these responses; JAK2 (but not JAK1/3) is also required for IL-17A-induced fibrogenic responses in fibroblasts. siRNA silencing of IL-17RA in normal and IPF fibroblasts, NF-κB inhibition, JAK2 siRNA and selective pharmacological inhibitors (AZD1480 vs tofacitinib), ECM protein measurement, myofibroblast marker assays American journal of physiology. Lung cellular and molecular physiology High 30604628
2019 IL-17B signals through IL-17RA and IL-17RB receptor subunits (like IL-25/IL-17E) to induce type 2 cytokine secretion from human innate type 2 lymphocytes, NKT, and Th2 cells; IL-17B can augment IL-33-driven type 2 responses. Receptor subunit blocking antibodies and genetic dependence studies in human primary lymphocytes, cytokine secretion assays Journal of immunology Medium 30770417
2025 IL-17RA in intestinal epithelial cells (IECs) suppresses EMT via restraint of EGFR/Src signaling; in macrophages, IL-17RA is required for Syk kinase activation upon dectin-1 engagement by fungi, enabling IL-18 release and protective CD8+ T cell anti-tumor immunity in colorectal cancer. Conditional IL-17RA deletion in IECs and macrophages, CRC mouse model, EGFR/Src pathway analysis, dectin-1/Syk signaling assays, IL-18 measurement, CD8+ T cell functional readouts, combinatorial immunotherapy experiments Immunity High 40023157
2016 IL-17RA in osteoclast precursors (conditional deletion with LysM-Cre) promotes osteoclast formation and subsequent bone resorption; IL-17ra conditional KO mice display increased trabecular bone mass due to reduced osteoclast precursor abundance. LysM-Cre conditional IL-17ra knockout, microCT bone analysis, histomorphometry, in vitro osteoclast differentiation assays Bone Medium 34973492
2024 Gingerenone A (GA) directly binds IL-17RA protein to inhibit IL-17 signaling; lentivirus-mediated IL-17RA/Act1 knockdown or co-treatment with brodalumab/ixekizumab impairs GA's protective effects against DSS-induced colitis, confirming IL-17RA as the molecular target. Pull-down assay, surface plasmon resonance, molecular dynamics simulation, lentiviral IL-17RA/Act1 knockdown, DSS-induced colitis mouse model, brodalumab/ixekizumab co-treatment Advanced science High 38639442
2018 IL-17A signaling through IL-17RA promotes MMP-2 and MMP-9 expression and NSCLC cell invasion via p38 MAPK pathway; p38 MAPK-specific inhibitor SB203580 suppresses IL-17RA-dependent migration and invasion; MMP-2/9 are downstream effectors of the IL-17RA/p38 axis. IL-17RA overexpression/knockdown in NSCLC cell lines, p38 MAPK inhibitor (SB203580), wound healing/Transwell invasion assays, Western blotting Molecular and cellular biochemistry Medium 30564960
2017 IL-17 regulates Cyr61, IL-23, GM-CSF, and RANKL expression in fibroblast-like synoviocytes via an IL-17RA/STAT-3 signaling cascade; IL-17RA knockdown reverses IL-17-induced SHP-2 upregulation and abolishes the osteoclastogenic potential of IL-17-treated FLS. siRNA knockdown of IL-17RA, STAT-3 inhibitor (S3I-201), co-culture osteoclast differentiation assays, Western blotting, TRAP staining Molecular immunology Medium 28898718
2019 IL-17RA/Act1 signaling is required for IL-17RA dimerization following IL-17A stimulation of airway smooth muscle cells; IL-17RA signaling also requires cell-type-specific Act1 for its direct effect on airway smooth muscle contraction. Cell type-specific deletion of IL-17R and Act1 in airway smooth muscle cells, Co-IP for complex formation Journal of immunology Medium 30683702
2019 Oxidative stress induces KLF4 transcription factor, which directly activates IL-17RA expression in retinal pigment epithelial cells, leading to IL-1β and IL-8 production; IL-17RA knockdown prevents OS-induced RPE apoptosis and inflammatory response. siRNA knockdown of IL-17RA and KLF4, promoter-binding assays, flow cytometry for apoptosis, AMD-like mouse model Free radical biology & medicine Medium 31881336
2024 IL-17A impedes efferocytosis in synovial macrophages via preferential activation of JAK/STAT-3/ADAM17 signaling axis, causing ADAM17-mediated shedding of MERTK; disruption of IL-17A/IL-17RA interaction (by cyanidin or IL-17RA silencing) abolishes ADAM17 expression, reduces MERTK shedding, and restores efferocytosis. IL-17RA silencing, cyanidin treatment, ADAM17 knockdown, MERTK shedding assays, efferocytosis functional assays, flow cytometry for macrophage phenotype, adjuvant-induced arthritis model International immunopharmacology Medium 38810305
2018 IL-17RA-/- mesenchymal stem cells (MSCs) lose immunosuppressive function in experimental autoimmune encephalomyelitis; IL-17RA-/- MSCs fail to reduce Th17 cell frequency and fail to generate CD4+CD25+Foxp3+ Tregs, correlating with reduced VCAM1, ICAM1, and PD-L1 expression on MSCs. IL-17RA-/- MSCs in EAE model, adoptive transfer, flow cytometry, gene expression analysis of immunosuppressive mediators Frontiers in immunology Medium 29760692
2005 IL-17 receptor (IL-17RA) is expressed on human airway smooth muscle cells; IL-17 induces CXCL-8 production via transcriptional mechanisms dependent on NF-κB and AP-1 binding sites in the CXCL-8 promoter; transcriptional inhibitor actinomycin D abolishes this response. IL-17R expression by RT-PCR, Western blotting, and surface immunostaining; CXCL-8 promoter reporter assays with wild-type and site-specific mutant constructs; actinomycin D inhibition Clinical immunology High 15893694
2009 IL-17RA signaling is required for weight loss, neutrophil migration, MPO accumulation, and oxidized phospholipid generation in the lung during influenza infection, but is dispensable for CD8+ T cell recruitment and viral clearance. IL-17RA-/- mice in influenza infection model, bronchoalveolar lavage cell counting, MPO measurement, oxidized phospholipid quantification, flow cytometric analysis of influenza-specific CD8+ T cells Journal of immunology High 19783685
2011 The pre-ligand assembly domain (PLAD) of IL-17RA mediates receptor-chain associations essential for IL-17 signaling; blocking IL-17RA PLAD with an Ig fusion protein reduces myocardial collagen production (MMP-2, MMP-9, TIMP-1, -2, collagen I/III) and improves diastolic cardiac function in spontaneously hypertensive rats. Lentiviral delivery of IL-17RA PLAD-Ig in spontaneously hypertensive rats, echocardiography, immunoblotting for MMP/TIMP/collagen, collagen quantitation Experimental and molecular pathology Medium 21530504
2018 IL-17RA signaling in CD8+ T cells is intrinsically required for maintenance of functional effector CD8+ T cells during Trypanosoma cruzi infection; in vitro recombinant IL-17 downregulates pro-apoptotic protein BAD and promotes CD8+ T cell survival. IL-17RA KO mice in T. cruzi infection model, adoptive transfer experiments, intracellular BAD expression analysis, PD-L1 blockade, transcriptomic profiling Frontiers in immunology High 30364284
2016 A linear 15-residue peptide antagonist (HAP) binds IL-17A and blocks IL-17RA binding; crystal structure shows two HAP molecules bind one IL-17A dimer symmetrically, with N-terminal portions forming a β-strand inserted between IL-17A monomers and C-terminal helix directly blocking the IL-17RA binding site on IL-17A. Phage-display peptide screening, saturation mutagenesis, X-ray crystallography of HAP:IL-17A complex, primary human cell cytokine inhibition assays Scientific reports High 27184415
2022 IL-17RA signaling in intestinal epithelium regulates secretory IgA responses against Citrobacter rodentium infection by controlling luminal hydrogen peroxide production and Tnfsf13 expression; reduced Tnfsf13 results in profound defects in generating pathogen-specific IgA+ antibody-secreting cells. Intestinal IL-17RA and IL-17RC conditional KO mice, C. rodentium infection model, luminal H2O2 measurement, Tnfsf13 expression analysis, IgA+ ASC quantification Journal of immunology Medium 33431657

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 307 24918373
2009 Critical role of IL-17RA in immunopathology of influenza infection. Journal of immunology (Baltimore, Md. : 1950) 296 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) 277 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 212 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 155 30604628
2012 The IL-17A/IL-17RA axis plays a proatherogenic role via the regulation of aortic myeloid cell recruitment. Circulation research 142 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 136 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 109 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 85 23956759
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
2024 Gingerenone A Attenuates Ulcerative Colitis via Targeting IL-17RA to Inhibit Inflammation and Restore Intestinal Barrier Function. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 73 38639442
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 68 21109515
2022 IL-17RA-signaling in Lgr5+ intestinal stem cells induces expression of transcription factor ATOH1 to promote secretory cell lineage commitment. Immunity 67 35081371
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
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 59 26871571
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
2021 Vaccine-driven lung TRM cells provide immunity against Klebsiella via fibroblast IL-17R signaling. Science immunology 57 34516780
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
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 56 30564960
2017 The flavonoid cyanidin blocks binding of the cytokine interleukin-17A to the IL-17RA subunit to alleviate inflammation in vivo. Science signaling 56 28223414
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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
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
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 52 33827787
2023 Candida albicans Promotes Oral Cancer via IL-17A/IL-17RA-Macrophage Axis. mBio 50 37067414
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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
2015 Association between single nucleotide polymorphisms IL17RA rs4819554 and IL17E rs79877597 and Psoriasis in a Spanish cohort. Journal of dermatological science 48 26347322
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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
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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 37 21145111
2022 FTO promotes liver inflammation by suppressing m6A mRNA methylation of IL-17RA. Frontiers in oncology 36 36172147
2018 IL-17RA-Signaling Modulates CD8+ T Cell Survival and Exhaustion During Trypanosoma cruzi Infection. Frontiers in immunology 35 30364284
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2016 IL17RA gene variants and anti-TNF response among psoriasis patients. The pharmacogenomics journal 35 27670766
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2012 IL-17A/IL-17RA interaction promoted metastasis of osteosarcoma cells. Cancer biology & therapy 34 23192273
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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
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2019 Secukinumab attenuates reactive astrogliosis via IL-17RA/(C/EBPβ)/SIRT1 pathway in a rat model of germinal matrix hemorrhage. CNS neuroscience & therapeutics 26 31020769
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2014 Toll-like receptor signaling directly increases functional IL-17RA expression in neuroglial cells. Clinical immunology (Orlando, Fla.) 26 25076485
2012 Association of single nucleotide polymorphisms on Interleukin 17 receptor A (IL17RA) gene with aspirin hypersensitivity in asthmatics. Human immunology 25 23220496
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
2016 Common variants in IL-17A/IL-17RA axis contribute to predisposition to and progression of congestive heart failure. Medicine 24 27399111
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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
2019 Intestinal IL-17R Signaling Constrains IL-18-Driven Liver Inflammation by the Regulation of Microbiome-Derived Products. Cell reports 23 31747600
2018 Locally Targeting the IL-17/IL-17RA Axis Reduced Tumor Growth in a Murine B16F10 Melanoma Model. Human gene therapy 23 30079767
2017 Interleukin-17 receptor A (IL-17RA) as a central regulator of the protective immune response against Giardia. Scientific reports 23 28819174
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
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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
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 16 34945130
2017 Artificial Macrocycles as IL-17A/IL-17RA Antagonists. MedChemComm 16 29750108
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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
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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
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