Affinage

IL17A

Interleukin-17A · UniProt Q16552

Length
155 aa
Mass
17.5 kDa
Annotated
2026-06-10
100 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL-17A is a secreted, disulfide-linked homodimeric cytokine produced by CD4+ T cells that acts as a master driver of inflammatory gene programs in stromal, epithelial, and neuronal target cells (PMID:7499828). It signals through a heterodimeric receptor in which the IL-17A dimer contacts IL-17RA directly while IL-17RC functions as a membrane-proximal co-receptor, an arrangement resolved by cryo-EM as a conserved 'tip-to-tip' receptor architecture (PMID:19575028, PMID:20012905, PMID:35863378); a peptide antagonist that occludes the IL-17RA-binding surface on IL-17A confirms this interface is required for activity (PMID:27184415). Receptor engagement recruits the common adaptor Act1 (TRAF3IP2) and downstream TRAF proteins (TRAF3/5/6) to activate NF-κB, MAPK, and C/EBP cascades that induce cytokines, chemokines, and antimicrobial effectors (PMID:24011563, PMID:31316496). Signal amplitude is tuned at the receptor: TRAF3 negatively regulates the pathway, and in keratinocytes FXYD3 competitively binds TRAF3 to displace it from IL-17RA, favoring IL-17RA–Act1 complex assembly and amplifying NF-κB/MAPK output in psoriatic inflammation (PMID:31316496, PMID:36693922). IL-17A transcription is gated by RORγt, whose activity is set by competing post-translational marks—SIRT6-mediated deacetylation at K192 enhances RORγt recruitment to the IL-17A promoter, whereas Ubc9-dependent SUMOylation recruits HDAC2 to repress it (PMID:30375383, PMID:38135684). In target tissues IL-17A drives diverse outcomes including metabolic reprogramming of fibroblastic reticular cells via IκBζ/CPT1A (PMID:30962593), ERK–NLRP3/caspase-1 pyroptosis in epithelial cells (PMID:35346673), and epithelial inflammatory aging (PMID:37291218). Beyond peripheral inflammation, IL-17A acts directly on cortical neurons through IL-17RA to dampen neuronal hyperactivity and promote sociability (PMID:31853066).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1995 High

    Established IL-17A as a secreted T-cell-derived cytokine with direct pro-inflammatory activity on stromal cells, answering what the cloned protein actually does.

    Evidence cDNA cloning from a CD4+ T cell library and recombinant protein assays measuring IL-6/IL-8 and ICAM-1 induction in fibroblasts

    PMID:7499828

    Open questions at the time
    • Receptor and signalling mediators not yet identified
    • No structural information on the cytokine
  2. 2009 High

    Defined the IL-17 receptor as an IL-17RA/IL-17RC complex using SEFIR/TILL domains and the Act1 adaptor, distinguishing it mechanistically from other cytokine receptor families.

    Evidence Structure-function and domain mutagenesis consolidated across studies; receptor subunit knockdown/overexpression with signalling reporters

    PMID:19575028 PMID:20012905

    Open questions at the time
    • Stoichiometry and 3D architecture of the complex unresolved
    • Relative roles of IL-17RA vs IL-17RC in ligand discrimination not fully defined
  3. 2013 High

    Identified Act1 as the common proximal adaptor coupling all IL-17 receptors to NF-κB, MAPK, and C/EBP effector programs, defining the canonical signalling axis.

    Evidence Genetic Act1 deletion with NF-κB/MAPK reporters and cytokine production assays

    PMID:24011563

    Open questions at the time
    • Mechanism of Act1 recruitment to the receptor not detailed here
    • Regulators of pathway amplitude not yet defined
  4. 2014 Medium

    Extended IL-17A action to the CNS by showing it directly activates ERK1/2 in oligodendrocyte progenitors and alters their cell-cycle exit and differentiation.

    Evidence Primary OPC stimulation with ERK phosphorylation Western blot, cell-cycle analysis, and cerebellar slice cultures

    PMID:25557204

    Open questions at the time
    • Receptor subunit dependence in OPCs not established
    • Single lab, in vitro/ex vivo only
  5. 2018 High

    Revealed transcriptional repression of IL-17A via RORγt SUMOylation that recruits HDAC2 to the promoter, identifying an inhibitory epigenetic checkpoint.

    Evidence Reciprocal Co-IP (Ubc9–RORγt), SUMO-defective mutants, HDAC2 ChIP at the IL-17 promoter, and conditional Hdac2 KO in T cells with colitis model

    PMID:30375383

    Open questions at the time
    • Signals controlling RORγt SUMOylation in vivo not defined
    • Interplay with activating modifications not addressed
  6. 2018 Medium

    Showed IL-17A promotes intestinal fibrosis by inducing epithelial-mesenchymal transition, linking the cytokine to tissue remodeling.

    Evidence IL-17A stimulation of IEC-6 cells with EMT marker readouts and anti-IL-17A antibody treatment in a TNBS fibrosis model

    PMID:30097894

    Open questions at the time
    • Direct vs indirect action on epithelium not separated
    • Receptor and signalling intermediates not mapped
  7. 2019 High

    Connected IL-17 signalling to metabolic reprogramming of stromal cells through IκBζ-driven CPT1A induction, explaining how it supports stromal proliferation in inflammation.

    Evidence Conditional IL-17RA KO in fibroblastic reticular cells with metabolic, cell-cycle, and gene expression assays in EAE and colitis models

    PMID:30962593

    Open questions at the time
    • Direct molecular link from receptor to IκBζ induction not detailed
    • Generalizability to other stromal cell types unknown
  8. 2019 High

    Demonstrated IL-17A acts directly on cortical neurons via IL-17RA to reduce hyperactivity and promote social behaviour, establishing a non-immune neuromodulatory role.

    Evidence Intra-S1DZ IL-17a injection, conditional neuronal IL-17Ra KO, in vivo electrophysiology, and behavioural assays

    PMID:31853066

    Open questions at the time
    • Downstream neuronal signalling mediators not identified
    • Whether IL-17RC participates in neurons unaddressed
  9. 2019 Medium

    Showed IL-17A is pro-inflammatory but antifibrogenic in skin, attenuating TGF-β/Wnt-driven collagen production, refining the tissue-context dependence of its effects.

    Evidence Organotypic skin and keratinocyte–fibroblast co-cultures with Wnt pathway analysis and collagen I quantification

    PMID:31276679

    Open questions at the time
    • Contrasts with profibrotic role in gut; reconciling mechanism unclear
    • Single lab
  10. 2019 Medium

    Implicated IL-17A/IL-17RA signalling in beta-cell dysfunction, linking the cytokine to inflammatory islet damage in type 1 diabetes.

    Evidence IL-17A stimulation of MIN6 cells, IL-17RA blocking antibody, and IL-17A KO in Akita diabetic mice with insulin and apoptosis readouts

    PMID:32903039

    Open questions at the time
    • Downstream signalling in beta cells not mapped
    • Single lab
  11. 2020 Medium

    Showed IL-17A drives M2 macrophage polarization indirectly via an epithelial intermediary, clarifying cell-type-specific routing of its activity.

    Evidence THP-1/endometriotic epithelial co-culture with flow cytometry plus a syngeneic mouse endometriosis model

    PMID:32117261

    Open questions at the time
    • Epithelial-derived mediators of polarization not identified
    • Single lab
  12. 2022 High

    Resolved the cryo-EM architecture of the IL-17A–IL-17RA–IL-17RC complex, establishing a conserved 'tip-to-tip' organizing principle and the direct vs co-receptor roles of the two subunits.

    Evidence Cryo-EM of binary and ternary complexes with single-molecule imaging and cell-based signalling assays

    PMID:35863378

    Open questions at the time
    • Conformational dynamics during signal initiation not captured
    • How receptor geometry recruits Act1 not structurally defined
  13. 2022 High

    Identified ERK–NLRP3/caspase-1 pyroptosis as an IL-17A-driven epithelial death pathway contributing to glucocorticoid resistance.

    Evidence RNA-seq, Western blot, ELISA, electron microscopy, and pharmacological ERK/NLRP3/caspase-1 inhibition in human nasal epithelial cells

    PMID:35346673

    Open questions at the time
    • Link from receptor to ERK activation not detailed
    • In vivo confirmation of the pyroptosis axis limited
  14. 2023 High

    Defined a receptor-proximal amplification mechanism in which FXYD3 displaces inhibitory TRAF3 from IL-17RA to favor Act1 complex assembly, explaining feed-forward psoriatic inflammation.

    Evidence Reciprocal Co-IP of FXYD3–TRAF3 and IL-17RA–Act1, FXYD3 keratinocyte-specific deletion, and IMQ psoriasis model

    PMID:36693922

    Open questions at the time
    • Whether FXYD3 regulation generalizes beyond keratinocytes unknown
    • Upstream control of FXYD3 expression not addressed
  15. 2023 High

    Showed SIRT6 deacetylates RORγt at K192 to enhance its promoter occupancy and IL-17A transcription, defining an activating epigenetic arm opposite to the SUMO/HDAC2 axis.

    Evidence Co-IP, K192 deacetylation mutagenesis, RORγt ChIP at the IL-17A promoter, and airway epithelial conditional Sirt6 KO in an asthma model

    PMID:38135684

    Open questions at the time
    • How SIRT6 activity is itself regulated in Th17 cells unclear
    • Balance between deacetylation and SUMOylation under physiologic stimuli not resolved
  16. 2023 Medium

    Connected IL-17 signalling to inflammatory skin aging via epidermal NF-κB, showing blockade delays age-related structural change.

    Evidence Single-cell RNA sequencing and in vivo IL-17 blockade in aging mice with NF-κB reporter readouts

    PMID:37291218

    Open questions at the time
    • Cellular source of IL-17 in aged skin not fully defined
    • Mechanism not reconstituted
  17. 2023 Medium

    Mapped chromatin- and STAT5-level control distinguishing IL-17A from IL-17F transcription at the shared locus, clarifying how the two cytokines are differentially produced.

    Evidence scRNA-seq, cytokine-capture combined with ChIP-seq/RNA-seq, H3K4me3 profiling, and STAT5 perturbation

    PMID:37244461

    Open questions at the time
    • Direct STAT5 binding events at IL17A vs IL17F not fully resolved
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the distinct receptor-proximal complexes assembled on the 'tip-to-tip' structure are translated into the divergent, tissue-specific outcomes (metabolic reprogramming, pyroptosis, EMT, neuromodulation) remains unresolved.
  • No unified model linking receptor geometry to context-dependent effector choice
  • Reconciliation of pro- vs antifibrotic roles across tissues lacking
  • Neuronal downstream signalling mediators unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 3
Localization
GO:0005576 extracellular region 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3
Partners
FXYD3IL17RAIL17RCTRAF3TRAF3IP2TRAF6
Complex memberships
IL-17RA–Act1 signalling complexIL-17RA–IL-17RC receptor complex

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Human IL-17 (hIL-17) was cloned from a CD4+ T cell library; the 155-amino-acid protein contains an N-terminal signal peptide and is secreted in glycosylated and non-glycosylated forms. Recombinant hIL-17 (as an Fc fusion protein or transfected-cell supernatant) induced IL-6 and IL-8 production and enhanced ICAM-1 surface expression on human fibroblasts. cDNA cloning, recombinant protein expression in CV1/EBNA cells, ELISA for IL-6/IL-8, flow cytometry for ICAM-1 Journal of immunology High 7499828
2009 IL-17A signals through a receptor complex composed of IL-17RA and IL-17RC subunits. The IL-17R family possesses unique structural motifs (SEFIR/TILL domains) and uses proximal signalling mediators distinct from other cytokine families, including Act1 as a common adaptor. Structure-function analysis, domain mutagenesis, signalling assays reviewed across multiple studies Nature reviews. Immunology High 19575028
2009 IL-17RC is required as a co-receptor subunit (together with IL-17RA) for IL-17A and IL-17F signalling; IL-17RC modulates the amplitude and specificity of IL-17-driven inflammatory responses. Receptor subunit knockdown/overexpression, signalling reporter assays Seminars in immunopathology Medium 20012905
2013 Act1 (encoded by TRAF3IP2) is a common proximal adaptor for all IL-17 family cytokine receptors; it mediates downstream activation of NF-κB, MAPKs, and C/EBPs to induce antimicrobial peptides, cytokines, and chemokines. Genetic deletion of Act1, signalling pathway assays (NF-κB, MAPK reporters), cytokine production assays Cytokine High 24011563
2019 IL-17 signalling in fibroblastic reticular cells (FRCs) induces expression of the transcriptional co-activator IκBζ, which mediates increased glucose uptake and upregulation of CPT1A (a rate-limiting enzyme of mitochondrial fatty acid oxidation), thereby metabolically reprogramming FRCs for proliferation and survival during inflammation. Conditional IL-17RA knockout in FRCs, metabolic assays (glucose uptake), gene expression (Cpt1a), cell-cycle and apoptosis analysis, EAE and colitis models Nature immunology High 30962593
2019 IL-17a acts directly on neurons in the primary somatosensory cortex dysgranular zone (S1DZ) via the IL-17Ra receptor to reduce neuronal hyperactivity and promote sociability; conditional deletion of IL-17Ra in S1DZ neurons abolishes the LPS-induced behavioural rescue in MIA offspring. Direct intra-S1DZ IL-17a injection, conditional neuronal IL-17Ra knockout, in vivo electrophysiology, behavioural assays Nature High 31853066
2022 Cryo-EM structures of IL-17A–IL-17RA binary and IL-17A–IL-17RA–IL-17RC ternary complexes reveal that the IL-17 receptor family uses a 'tip-to-tip' architecture as a conserved organizing principle; IL-17A contacts IL-17RA directly, while IL-17RC functions as a co-receptor at the membrane-proximal level. Cryo-electron microscopy, single-molecule imaging, cell-based signalling assays Nature High 35863378
2016 Crystal structure of IL-17A dimer bound to a 15-residue peptide antagonist (HAP) shows that two HAP molecules bind symmetrically: the N-terminal β-strand inserts between the two IL-17A monomers while the C-terminal α-helix directly occludes the IL-17RA-binding site on IL-17A. Phage-display screening, saturation mutagenesis, X-ray crystallography, primary human cell cytokine assays Scientific reports High 27184415
2018 SUMOylation of the transcription factor ROR-γt (mediated by SUMO-conjugating enzyme Ubc9 at a conserved GKAE motif) suppresses IL-17A expression by facilitating HDAC2 recruitment to the IL-17 promoter, thereby repressing transcription. Conditional deletion of HDAC2 in CD4+ T cells elevates IL-17 expression and worsens colitis. Co-IP (Ubc9–ROR-γt interaction), SUMOylation-defective ROR-γt mutants, chromatin immunoprecipitation (HDAC2 at IL-17 promoter), conditional Hdac2 knockout in T cells, colitis transfer model Nature communications High 30375383
2019 TRAF proteins (including TRAF3, TRAF5, TRAF6) are recruited downstream of IL-17 receptor engagement to mediate activation of NF-κB, MAPK and other signalling cascades; TRAF3 negatively regulates IL-17 signalling. Biochemical interaction assays, TRAF knockout/knockdown, downstream signalling reporters reviewed across primary studies Frontiers in immunology Medium 31316496
2022 IL-17A induces pyroptosis in human nasal epithelial cells primarily through the ERK–NLRP3/caspase-1 signalling pathway, increasing IL-1β and IL-18 secretion; this pyroptotic mechanism contributes to glucocorticoid resistance by altering glucocorticoid receptor-α and glucocorticoid receptor-β expression. RNA sequencing, Western blotting, ELISA, electron microscopy of IL-17A-treated hNECs, pharmacological inhibition of ERK/NLRP3/caspase-1, GR-α/GR-β expression assays The Journal of allergy and clinical immunology High 35346673
2023 SIRT6 epigenetically regulates IL-17A transcription by directly interacting with RORγt and deacetylating it at lysine 192 via its PPXY motifs, promoting RORγt recruitment to the IL-17A gene promoter and enhancing IL-17A expression; airway epithelial cell-specific deletion of Sirt6 reduces IL-17A-driven inflammation and remodelling in a mouse asthma model. Co-IP (SIRT6–RORγt), deacetylation assay (K192 mutagenesis), ChIP (RORγt at IL-17A promoter), conditional Sirt6 knockout mice, allergen-challenge model Nature communications High 38135684
2023 FXYD3 enhances IL-17A signalling in keratinocytes by competitively binding TRAF3, displacing it from the IL-17RA receptor and thereby facilitating formation of the IL-17RA–ACT1 complex; this amplifies NF-κB and MAPK activation, creating a positive feedback loop that promotes psoriatic inflammation. Co-IP (FXYD3–TRAF3, IL-17RA–ACT1 complex), FXYD3 keratinocyte-specific deletion, IMQ-induced psoriasis mouse model, NF-κB/MAPK signalling assays Cellular & molecular immunology High 36693922
2023 IL-17 signals through NF-κB in epidermal cells in aged skin, impairing homeostatic epithelial functions while promoting an inflammatory state; in vivo blockade of IL-17 signalling during aging reduces this proinflammatory NF-κB activity and delays age-related skin structural changes. Single-cell RNA sequencing, in vivo IL-17 signalling blockade in aging mice, NF-κB pathway reporter assays in epidermal cells Nature aging Medium 37291218
2014 IL-17A activates ERK1/2 within 15 minutes in primary murine oligodendrocyte progenitor cells (OPCs), induces chemokine expression, and promotes OPC exit from cell cycle and differentiation; proteolipid protein expression increased in cerebellar slice cultures treated with IL-17A. Primary OPC culture stimulation, ERK1/2 phosphorylation assay (Western blot), cell cycle analysis, cerebellar slice culture assay Glia Medium 25557204
2018 IL-17A promotes intestinal fibrosis through induction of epithelial-mesenchymal transition (EMT) in intestinal epithelial cells, reducing E-cadherin and increasing vimentin, snail, and α-SMA expression; anti-IL-17A treatment in a TNBS mouse model reduced intestinal fibrosis by decreasing EMT markers. In vitro IEC-6 cell stimulation with IL-17A, EMT marker gene expression, in vivo anti-IL-17A antibody treatment in TNBS colitis/fibrosis mouse model Digestive diseases and sciences Medium 30097894
2020 IL-17A indirectly induces M2 macrophage polarization markers (CCL17, CD206) in a co-culture system by first acting on endometriotic epithelial cells rather than macrophages directly; in a syngeneic mouse model of endometriosis, IL-17A treatment increased peritoneal macrophage recruitment with M2 phenotype. THP-1/endometriotic epithelial co-culture with IL-17A, flow cytometry for M2 markers, syngeneic mouse endometriosis model with IL-17A treatment Frontiers in immunology Medium 32117261
2023 STAT5 signalling differentially regulates IL-17A and IL-17F expression in Th17 cells: IL-2/STAT5 signalling has opposing effects on IL-17A versus IL-17F transcription, and the IL17A-F locus displays a broad H3K4me3 region reflecting high chromatin accessibility. Higher IL-17F expression correlates with greater cell proliferation. Single-cell RNA sequencing, cytokine-capture combined with ChIP-seq and RNA-seq, H3K4me3 ChIP-seq, STAT5 pathway perturbation The Journal of allergy and clinical immunology Medium 37244461
2019 In organotypic full-skin cultures and keratinocyte–fibroblast co-culture systems, IL-17A strongly promotes pro-inflammatory gene expression but does not directly induce collagen gene expression; IL-17A attenuates TGF-β-induced Wnt signalling and decreases collagen I protein production, supporting a pro-inflammatory but antifibrogenic role in skin. Organotypic skin culture, keratinocyte-conditioned media applied to fibroblasts, gene expression arrays, protein-level collagen I quantification, Wnt signalling pathway analysis The Journal of investigative dermatology Medium 31276679
2019 IL-17 signalling through IL-17RA in MIN6 mouse insulin-producing cells enhances inflammatory cytokine production, oxidative stress, and apoptosis while attenuating insulin secretion; blockade of IL-17RA abolishes these effects. IL-17A deficiency alleviates hyperglycemia and hypoinsulinemia in Akita T1D mice. IL-17A stimulation of MIN6 cells, IL-17RA blocking antibody, IL-17A knockout (Akita mice), insulin ELISA, apoptosis and oxidative stress assays Experimental biology and medicine Medium 32903039

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 IL-17 and Th17 Cells. Annual review of immunology 3956 19132915
2009 Structure and signalling in the IL-17 receptor family. Nature reviews. Immunology 1212 19575028
2012 Targeting IL-17 and TH17 cells in chronic inflammation. Nature reviews. Drug discovery 1135 23023676
2003 Interleukin-17 family and IL-17 receptors. Cytokine & growth factor reviews 722 12651226
1995 Human IL-17: a novel cytokine derived from T cells. Journal of immunology (Baltimore, Md. : 1950) 665 7499828
2017 IL-17 Signaling: The Yin and the Yang. Trends in immunology 640 28254169
2013 IL-17 family: cytokines, receptors and signaling. Cytokine 473 24011563
2019 IL-17 receptor-based signaling and implications for disease. Nature immunology 438 31745337
2013 IL-17 cytokines in immunity and inflammation. Emerging microbes & infections 424 26038490
2018 The IL-17 Family of Cytokines in Psoriasis: IL-17A and Beyond. Frontiers in immunology 384 30127781
2023 The IL-17 family in diseases: from bench to bedside. Signal transduction and targeted therapy 329 37816755
2016 IL-17 in Chronic Inflammation: From Discovery to Targeting. Trends in molecular medicine 322 26837266
2014 IL-17 in severe asthma. Where do we stand? American journal of respiratory and critical care medicine 308 25162311
2008 An overview of IL-17 function and signaling. Cytokine 275 18701318
2010 IL-17 and Th17 cells in tuberculosis. Cytokine & growth factor reviews 263 21075039
2004 IL-17 cytokine family. The Journal of allergy and clinical immunology 262 15577820
2008 IL-23 and IL-17 in tuberculosis. Cytokine 232 18218322
2011 Recent advances in the IL-17 cytokine family. Current opinion in immunology 231 21852080
2019 IL-17a promotes sociability in mouse models of neurodevelopmental disorders. Nature 225 31853066
2020 COVID-19: a case for inhibiting IL-17? Nature reviews. Immunology 224 32358580
2014 IL-17 and Th17 cells in atherosclerosis: subtle and contextual roles. Arteriosclerosis, thrombosis, and vascular biology 223 25234818
2020 IL-17 and immunologically induced senescence regulate response to injury in osteoarthritis. The Journal of clinical investigation 211 32955487
2010 Role of IL-17 and Th17 cells in liver diseases. Clinical & developmental immunology 207 21197451
2010 IL-17 and IL-22: siblings, not twins. Trends in immunology 202 20691634
2014 Directing traffic: IL-17 and IL-22 coordinate pulmonary immune defense. Immunological reviews 163 24942687
2017 IL-17 in the lung: the good, the bad, and the ugly. American journal of physiology. Lung cellular and molecular physiology 157 28860146
2020 IL-17A in Psoriasis and Beyond: Cardiovascular and Metabolic Implications. Frontiers in immunology 150 32010143
2010 IL-17 in obesity and adipogenesis. Cytokine & growth factor reviews 149 21084215
2013 IL-17 targeted therapies for psoriasis. Expert opinion on investigational drugs 133 23731078
2013 Role of IL-17 in psoriasis and psoriatic arthritis. Clinical reviews in allergy & immunology 131 22362575
2010 IL-17 in protective immunity to intracellular pathogens. Virulence 129 21178483
2018 IL-17 in the immunopathogenesis of spondyloarthritis. Nature reviews. Rheumatology 121 30006601
2020 IL-17 in inflammatory skin diseases psoriasis and hidradenitis suppurativa. Clinical and experimental immunology 119 32379344
2006 The IL-17 cytokine family. Vitamins and hormones 117 17027518
2014 Cellular sources of IL-17 in psoriasis: a paradigm shift? Experimental dermatology 113 25039885
2008 The IL-17 cytokine family and their role in allergic inflammation. Current opinion in immunology 111 18832032
2013 Th17 cells and IL-17 a--focus on immunopathogenesis and immunotherapeutics. Seminars in arthritis and rheumatism 110 24157091
2019 Systemic effects of IL-17 in inflammatory arthritis. Nature reviews. Rheumatology 107 31227819
2020 IL-17A Modulates Peritoneal Macrophage Recruitment and M2 Polarization in Endometriosis. Frontiers in immunology 105 32117261
2017 Maternal IL-17A in autism. Experimental neurology 100 28455196
2016 T cells and IL-17 in lupus nephritis. Clinical immunology (Orlando, Fla.) 98 27109641
2012 Mucocutaneous candidiasis: the IL-17 pathway and implications for targeted immunotherapy. Arthritis research & therapy 98 22838497
2008 IL-17 and therapeutic kynurenines in pathogenic inflammation to fungi. Journal of immunology (Baltimore, Md. : 1950) 97 18390695
2010 The IL-17 family cytokines in immunity and disease. Journal of clinical immunology 93 20177959
2017 The Role of IL-17 in Protection against Mucosal Candida Infections. Journal of fungi (Basel, Switzerland) 90 29371568
2009 IL-17RC: a partner in IL-17 signaling and beyond. Seminars in immunopathology 88 20012905
2019 IL-17 metabolically reprograms activated fibroblastic reticular cells for proliferation and survival. Nature immunology 86 30962593
2019 TRAF Regulation of IL-17 Cytokine Signaling. Frontiers in immunology 79 31316496
2021 The Role of IL-17 Cytokines in Psoriasis. ImmunoTargets and therapy 78 34853779
2013 IL-17 in lung disease: friend or foe? Thorax 75 23604380
2022 IL-17A mediates pyroptosis via the ERK pathway and contributes to steroid resistance in CRSwNP. The Journal of allergy and clinical immunology 74 35346673
2019 Anti IL-17 in psoriasis. Expert review of clinical immunology 74 31603358
2012 The IL-17 differentiation pathway and its role in transplant outcome. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 72 22226114
2013 IL-17 in psoriasis: implications for therapy and cardiovascular co-morbidities. Cytokine 66 23562549
2010 Genomics of fish IL-17 ligand and receptors: a review. Fish & shellfish immunology 66 21134467
2022 Organizing structural principles of the IL-17 ligand-receptor axis. Nature 64 35863378
2019 IL-17 and IL-22 Promote Keratinocyte Stemness in the Germinative Compartment in Psoriasis. The Journal of investigative dermatology 63 30684548
2018 IL-17A Promotes Initiation and Development of Intestinal Fibrosis Through EMT. Digestive diseases and sciences 63 30097894
2023 Targeting lymphoid-derived IL-17 signaling to delay skin aging. Nature aging 59 37291218
2019 HIF-1α regulates IL-1β and IL-17 in sarcoidosis. eLife 58 30946009
2019 IL-17A is not a treatment target in progressive vitiligo. Pigment cell & melanoma research 56 31063266
2016 Cross-Disease Transcriptomics: Unique IL-17A Signaling in Psoriasis Lesions and an Autoimmune PBMC Signature. The Journal of investigative dermatology 56 27206706
2018 SUMOylation of ROR-γt inhibits IL-17 expression and inflammation via HDAC2. Nature communications 55 30375383
2008 Regulatory T cells and the induction of IL-17. Mucosal immunology 55 19079228
2014 The role of IL-17 in psoriasis. The Journal of dermatological treatment 54 24552504
2015 Regulation of IL-17 in autoimmune diseases by transcriptional factors and microRNAs. Frontiers in genetics 53 26236331
2017 Is there a role for IL-17 in the pathogenesis of systemic sclerosis? Immunology letters 52 28919455
2015 The IL-23 to IL-17 cascade inflammation-related cancers. Clinical and experimental rheumatology 51 26457610
2019 The advent of IL-17A blockade in ankylosing spondylitis: secukinumab, ixekizumab and beyond. Expert review of clinical immunology 50 30576610
2024 Targeting STING in dendritic cells alleviates psoriatic inflammation by suppressing IL-17A production. Cellular & molecular immunology 48 38806624
2021 Role of IL-17 in atopy-A systematic review. Clinical and translational allergy 48 34429872
2016 Inhibiting complex IL-17A and IL-17RA interactions with a linear peptide. Scientific reports 48 27184415
2024 IL-17 in wound repair: bridging acute and chronic responses. Cell communication and signaling : CCS 47 38802947
2023 Epithelial SIRT6 governs IL-17A pathogenicity and drives allergic airway inflammation and remodeling. Nature communications 47 38135684
2020 IL-17 Signaling in the Tumor Microenvironment. Advances in experimental medicine and biology 46 32060887
2016 Targeting IL-17 in autoimmunity and inflammation. Archives of pharmacal research 46 27576555
2014 IL-17 and infections. Actas dermo-sifiliograficas 46 25398490
2016 Effect of IL-17 receptor A blockade with brodalumab in inflammatory diseases. Rheumatology (Oxford, England) 44 27856660
2014 IL-17A activates ERK1/2 and enhances differentiation of oligodendrocyte progenitor cells. Glia 44 25557204
2014 Pathogenic role of IL-17 in psoriasis and psoriatic arthritis. Actas dermo-sifiliograficas 42 25398488
2020 IL-17E (IL-25) and IL-17A Differentially Affect the Functions of Human Keratinocytes. The Journal of investigative dermatology 41 31958433
2017 IL-17 for therapy. Journal of dermatological science 41 28633806
2013 Inhibition of IL-17 as a pharmacological approach for IBD. International reviews of immunology 41 23886112
2022 The Yin and Yang of IL-17 in Systemic Sclerosis. Frontiers in immunology 40 35603223
2020 IL-17A and IL-17F orchestrate macrophages to promote lung cancer. Cellular oncology (Dordrecht, Netherlands) 39 32227296
2023 Th17 Cells and IL-17A in Ischemic Stroke. Molecular neurobiology 38 37884768
2018 IL-17 can be protective or deleterious in murine pneumococcal pneumonia. PLoS pathogens 38 29813133
2021 Pharmacological Rationale for Targeting IL-17 in Asthma. Frontiers in allergy 36 35387016
2020 IL-17A is involved in diabetic inflammatory pathogenesis by its receptor IL-17RA. Experimental biology and medicine (Maywood, N.J.) 36 32903039
2019 IL-17A Dissociates Inflammation from Fibrogenesis in Systemic Sclerosis. The Journal of investigative dermatology 36 31276679
2015 Contribution of the IL-17 Pathway to Psoriasis and Psoriatic Arthritis. Current rheumatology reports 36 26209291
2023 Differential regulation of IL-17A and IL-17F via STAT5 contributes to psoriatic disease. The Journal of allergy and clinical immunology 35 37244461
2020 IL-17D: A Less Studied Cytokine of IL-17 Family. International archives of allergy and immunology 35 32516792
2023 IL-17 in osteoarthritis: A narrative review. Open life sciences 34 37854319
2020 The Interrelationship Between Diabetes, IL-17 and Bone Loss. Current osteoporosis reports 34 32002770
2019 The Role of IL-17 in Papulopustular Rosacea and Future Directions. Journal of cutaneous medicine and surgery 34 31402691
2017 IL-17 and related cytokines involved in systemic sclerosis: Perspectives. Autoimmunity 34 29256263
2017 Targeting IL-17 in psoriatic arthritis. European journal of rheumatology 34 29308283
2023 FXYD3 enhances IL-17A signaling to promote psoriasis by competitively binding TRAF3 in keratinocytes. Cellular & molecular immunology 33 36693922
2022 IL-17: an important pathogenic factor in endometriosis. International journal of medical sciences 33 35582411

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