Affinage

IL17F

Interleukin-17F · UniProt Q96PD4

Length
163 aa
Mass
18.0 kDa
Annotated
2026-06-10
100 papers in source corpus 28 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL-17F is a proinflammatory cytokine produced by Th17 cells that drives neutrophilic tissue inflammation and antimicrobial defense through a dedicated IL-17 receptor signaling axis (PMID:18411338, PMID:28813677). It exists as a disulfide-linked homodimer and also pairs with IL-17A to form an IL-17A/F heterodimer, all of which are secreted by differentiated Th17 cells (PMID:17452998, PMID:18025225). IL-17F signals through the IL-17RA/IL-17RC receptor heterodimer—binding IL-17RC with affinity comparable to IL-17A while engaging IL-17RA distinctly—and a crystal structure of the IL-17RC extracellular domain bound to IL-17F shows a symmetrical 2:1 IL-17RC:cytokine complex that competes with IL-17RA, defining a basis for IL-17RA-independent signaling (PMID:18684971, PMID:32187518). IL-17F-induced gene expression requires IL-17RA, IL-17RC, the adaptor Act1, and TRAF6, and IL-17RC is induced into complex with IL-17RA rather than pre-associated (PMID:18411338, PMID:20231694). Downstream, IL-17F activates the Raf1-MEK-ERK-p90RSK/MSK1-CREB cascade and NF-κB/IκBζ-dependent transcription in epithelial and stromal cells to induce chemokines (CXCL10/IP-10, IL-8, CXCL1, CXCL5, CCL20), cytokines (IL-6, IL-11), and antimicrobial peptides (DEFB4, S100A7) (PMID:17418381, PMID:19251839, PMID:27576147, PMID:27030744). In vivo, IL-17F plays roles distinct from and sometimes opposing IL-17A, driving allergic and infection-associated airway neutrophilia, DSS colitis (via regulation of the intestinal microbiota and Treg balance), and crescentic glomerulonephritis through CXCL1/CXCL5-mediated neutrophil recruitment (PMID:18411338, PMID:29915298, PMID:27030744, PMID:30655284). Its expression at the shared IL17A–IL17F locus is governed by a Th17-lineage cis-regulatory element (CNS2) that recruits p300 and JMJD3 and bears H3K4me3/H3K27 acetylation marks, with STAT5/IL-2 and prostaglandin/cytokine inputs differentially partitioning IL-17F versus IL-17A output (PMID:17218320, PMID:22244845, PMID:23800789). A natural His161Arg variant is signaling-dead and dominantly blocks wild-type IL-17F, acting as an endogenous antagonist (PMID:16630936).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2006 High

    Established that IL-17F is a functional epithelial-activating cytokine and identified a natural loss-of-function variant, revealing both its signaling output and a mechanism of endogenous antagonism.

    Evidence Recombinant wild-type and H161R IL-17F on bronchial epithelial cells with MAPK and cytokine/chemokine readouts

    PMID:16630936

    Open questions at the time
    • Did not define the receptor or adaptor requirements
    • Structural basis of H161R antagonism not resolved
  2. 2007 Medium

    Defined the proximal MAPK signaling route by which IL-17F drives chemokine output, establishing the Raf1-MEK-ERK-p90RSK-CREB cascade.

    Evidence Kinase inhibitors, dominant-negative Raf1, and siRNA of p90RSK/CREB in bronchial epithelial cells measuring IP-10

    PMID:17418381

    Open questions at the time
    • Receptor engagement upstream of Raf1 not addressed
    • Single cell type
  3. 2007 High

    Showed that IL-17A and IL-17F form a heterodimer in addition to homodimers and are co-secreted by Th17 cells, and that IL-17F locus activation is epigenetically programmed during Th17 differentiation.

    Evidence Overexpression/recombinant protein assays plus ChIP for histone marks at the IL-17/IL-17F locus in Th17 cells

    PMID:17218320 PMID:17452998 PMID:18025225

    Open questions at the time
    • Receptor specificity of the heterodimer not yet defined
    • Regulatory element driving locus marks not identified
  4. 2008 High

    Identified the receptor and adaptor requirements for IL-17F signaling and demonstrated non-redundant in vivo roles distinct from IL-17A in airway and intestinal inflammation.

    Evidence IL-17F knockout and transgenic mice, genetic knockouts of IL-17RA/TRAF6/Act1 in vitro, SPR binding, and allergen/DSS colitis models

    PMID:18411338 PMID:18684971

    Open questions at the time
    • Stoichiometry of receptor binding unresolved
    • Mechanism of opposing IL-17A vs IL-17F colitis phenotypes unclear
  5. 2009 Medium

    Extended the MAPK signaling model to IL-11 induction and showed reciprocal regulation in which IL-17A suppresses IL-17F production through IL-17RA.

    Evidence MSK1/CREB siRNA and inhibitors in epithelial cells; Il17a-/- mice and IL-17RA-deficient cells measuring IL-17F

    PMID:19251839 PMID:19542376

    Open questions at the time
    • Molecular basis of IL-17A-mediated feedback on IL-17F transcription not defined
  6. 2010 High

    Established IL-17RC as absolutely required for IL-17F signaling and showed the receptor complex is ligand-induced rather than pre-formed, with the SEFIR domain essential for transduction but not assembly.

    Evidence Il17rc-/- mice, cell-surface complex-formation assays, and SEFIR domain mutagenesis

    PMID:20231694

    Open questions at the time
    • Quantitative receptor stoichiometry not resolved at this stage
  7. 2012 High

    Identified the CNS2 cis-regulatory element as the locus-control mechanism that physically contacts the Il17/Il17f promoters and recruits histone-modifying enzymes to enable selective Th17 transcription.

    Evidence CNS2 targeted deletion in mice with chromosome-conformation assays and ChIP for p300 and JMJD3

    PMID:22244845

    Open questions at the time
    • How CNS2 differentially partitions IL-17F vs IL-17A output not fully defined
  8. 2016 High

    Resolved the mechanism of IL-17F-driven tissue injury in glomerulonephritis as CXCL1/CXCL5-mediated neutrophil recruitment, and demonstrated requirement in NAFLD inflammation.

    Evidence Il17f-/- mice, neutralizing antibodies, adoptive transfer, neutrophil depletion in nephritis models; MCDD diet model

    PMID:26895034 PMID:27030744

    Open questions at the time
    • Cell-type-specific source of pathogenic IL-17F in chronic models not fully dissected
  9. 2017 High

    Defined an IL-17RA-independent IL-17F/IL-17RC signaling axis on epithelium with context-dependent protective vs pathogenic outcomes, and identified IκBζ as a transcriptional mediator of psoriasis-associated genes.

    Evidence Il17ra-/-/Il17a-/-/Il17f-/- mice in airway infection/inflammation models; IκBζ siRNA and p38/NF-κB inhibitors in keratinocytes

    PMID:27576147 PMID:28813677

    Open questions at the time
    • Structural basis of IL-17RA-independent signaling not yet shown
    • Determinants of protective vs pathogenic outcome unclear
  10. 2018 High

    Showed IL-17F shapes the intestinal microbiota and Treg balance, providing a mechanistic basis for its selective pathogenicity in colitis distinct from IL-17A.

    Evidence Il17f-/- mice, adoptive transfer into Rag2-/-, anti-IL-17F antibody, and 16S microbiota analysis

    PMID:29915298

    Open questions at the time
    • Direct antimicrobial-protein targets mediating microbiota shifts not enumerated
  11. 2020 High

    Provided the structural mechanism of receptor engagement, showing IL-17RC forms a symmetric 2:1 complex with IL-17F that competes with IL-17RA, rationalizing IL-17RA-independent signaling.

    Evidence X-ray crystallography of IL-17RC ectodomain:IL-17F complex with SPR/ITC biophysics

    PMID:32187518

    Open questions at the time
    • How the 2:1 complex transduces signal in the absence of IL-17RA not resolved
    • No structure of the full signaling complex
  12. 2023 Medium

    Refined the picture of differential IL-17A vs IL-17F regulation in human disease, linking distinct T cell populations, STAT5/IL-2 signaling, and locus epigenetic architecture to selective IL-17F output.

    Evidence Single-cell RNA-seq, cytokine-capture with ChIP-seq/RNA-seq on psoriatic skin and in vitro culture

    PMID:37244461

    Open questions at the time
    • Causal regulators distinguishing the two genes not fully isolated
    • Single-lab dataset

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the IL-17F/IL-17RC 2:1 complex transduces signal independently of IL-17RA, and what determines whether IL-17F output is protective versus pathogenic in a given tissue, remains unresolved.
  • No structure of an IL-17RA-independent signaling-competent complex
  • Tissue-context switch between protective and pathogenic IL-17F responses unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 7 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4
Partners
ACT1IL17AIL17RAIL17RCTRAF6

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 IL-17A and IL-17F form not only homodimers but also a heterodimeric cytokine (IL-17A/F) when co-expressed; fully differentiated mouse Th17 cells naturally secrete all three forms. Recombinant IL-17A/F exhibits intermediate potency in inducing IL-6 and CXCL1 compared to homodimers. IL-17A/F regulation of IL-6 and CXCL1 is dependent on IL-17RA and TRAF6. Overexpression in 293T cells, recombinant protein assays in vitro, Th17 cell culture, siRNA/antibody blockade of IL-17RA and TRAF6 Cell research High 17452998 18025225
2008 The IL-17F/IL-17A heterodimeric cytokine signals through the IL-17RA/IL-17RC receptor complex. Surface plasmon resonance shows IL-17F binds IL-17RC with comparable affinity to IL-17A, but the three cytokines bind IL-17RA with different affinities. IL-17F activity is preferentially inhibited by soluble IL-17RC, whereas IL-17A activity is preferentially inhibited by soluble IL-17RA; combined soluble receptors are required to block IL-17F/IL-17A heterodimer. siRNA knockdown of IL-17RA and IL-17RC, neutralizing antibodies, surface plasmon resonance binding assays, soluble receptor blockade Journal of immunology High 18684971
2008 IL-17F proinflammatory gene expression in vitro requires IL-17 receptor A (IL-17RA), TRAF6, and Act1. In vivo, IL-17F overexpression in lung epithelium caused lymphocyte/macrophage infiltration and mucus hyperplasia. IL-17F-deficient mice (but not IL-17-deficient mice) had defective airway neutrophilia after allergen challenge; IL-17F deficiency also resulted in reduced colitis caused by DSS, whereas IL-17 knockout mice developed more severe disease. IL-17F knockout mice, IL-17F transgenic lung overexpression, in vitro cytokine stimulation with genetic knockouts, allergen challenge model, DSS colitis model The Journal of experimental medicine High 18411338
2010 IL-17RC is absolutely required for IL-17A, IL-17F, and IL-17A/F signaling both in vitro and in vivo, as demonstrated using Il-17rc-deficient mice. IL-17RC does not pre-associate with IL-17RA on the cell surface; rather, IL-17A induces formation of an IL-17RC/IL-17RA complex. The SEFIR domain of IL-17RC is not required for complex formation but is essential for IL-17A signal transduction. Il-17rc-deficient mice, in vitro signaling assays, cell surface co-immunoprecipitation/complex formation assays, domain mutagenesis (SEFIR domain), EAE disease model Journal of immunology High 20231694
2006 The IL-17F His161Arg (H161R) variant lacks the ability to activate the MAPK pathway, cytokine production, and chemokine production in bronchial epithelial cells unlike wild-type IL-17F. Furthermore, the H161R variant blocks induction of IL-8 expression by wild-type IL-17F, functioning as a natural IL-17F antagonist. Recombinant wild-type and H161R mutant IL-17F proteins, in vitro stimulation of bronchial epithelial cells, MAPK pathway assays, cytokine/chemokine ELISA The Journal of allergy and clinical immunology High 16630936
2007 THi (Th17) cell differentiation is accompanied by selective histone H3 acetylation and Lys-4 tri-methylation specifically at IL-17 and IL-17F gene promoters. TGF-β and IL-6 synergistically promoted histone acetylation on these promoters at early T cell activation. Multiple noncoding conserved sequences within the IL-17–IL-17F locus also showed lineage-specific histone H3 hyperacetylation in Th17 cells. Chromatin immunoprecipitation (ChIP) in Th17, Th1, and Th2 cells; cytokine stimulation (TGF-β + IL-6) The Journal of biological chemistry Medium 17218320
2012 A cis-regulatory element (CNS2) physically interacts with both Il17 and Il17f gene promoters and is sufficient for regulating their selective transcription in Th17 cells. Targeted deletion of CNS2 impaired RORγt-driven IL-17 expression and substantially decreased IL-17F production, associated with defective chromatin remodeling and reduced recruitment of histone-modifying enzymes p300 and JMJD3 to the locus. CNS2 targeted deletion in mice, chromosome conformation/physical interaction assay, ChIP for p300 and JMJD3, in vitro Th17 differentiation, EAE model Immunity High 22244845
2007 IL-17F induces IP-10 (CXCL10) expression in bronchial epithelial cells through the Raf1-MEK1/2-ERK1/2-p90RSK-CREB signaling pathway. MEK inhibitors (PD98059, U0126), Raf1 kinase inhibitor, and dominant-negative Raf1 blocked IP-10 production. IL-17F phosphorylated p90RSK and CREB; siRNA knockdown of p90RSK or CREB inhibited IP-10 expression. Bronchial epithelial cell culture, pharmacological kinase inhibitors, dominant-negative Raf1 overexpression, siRNA knockdown of p90RSK and CREB, ELISA, RT-PCR The Journal of allergy and clinical immunology Medium 17418381
2009 IL-17F induces IL-11 expression in bronchial epithelial cells via the Raf1-MEK1/2-ERK1/2-MSK1-CREB signaling pathway. IL-17F phosphorylated MSK1; MEK inhibitors blocked MSK1 phosphorylation. siRNA knockdown of MSK1 inhibited CREB activation, and siRNAs targeting MSK1 and CREB blocked IL-11 expression. Co-stimulation with IL-4 and IL-13 augmented IL-17F-induced IL-11. Bronchial epithelial cell culture, MEK/Raf1 inhibitors, dominant-negative Raf1, siRNA knockdown of MSK1 and CREB, phosphorylation assays American journal of physiology. Lung cellular and molecular physiology Medium 19251839
2008 IL-17F induces IL-8 production in normal human epidermal keratinocytes through activation of the ERK1/2 (MEK) pathway. Selective MEK inhibitors significantly inhibited IL-17F-induced IL-8 production. In mouse skin, intradermal IL-17F injection induced IL-8 mRNA and ERK1/2 phosphorylation, and caused marked dermal neutrophilia that was inhibited by anti-IL-8 antibody. Keratinocyte cell culture with recombinant IL-17F, MEK inhibitors, in vivo mouse skin injection, anti-IL-8 neutralizing antibody, RT-PCR, ELISA, histology The Journal of investigative dermatology Medium 18830271
2010 IL-17F induces IL-6 production in normal human epidermal keratinocytes in a time-dependent manner, which is attenuated by a chimeric inhibitor blocking the IL-17 receptor. IL-17F-induced IL-6 was higher than that induced by TNF-α or IL-17A. In mouse skin, intradermal IL-17F injection increased IL-6 mRNA expression 3.2-fold. Keratinocyte cell culture with recombinant IL-17F, IL-17 receptor chimeric inhibitor, in vivo mouse skin injection, RT-PCR, ELISA Archives of dermatological research Medium 20148256
2017 IL-17F stimulation of human keratinocytes induces IκBζ expression at mRNA and protein levels via p38 MAPK and NF-κB signaling pathways. IκBζ silencing by siRNA revealed it is a key mediator of specific IL-17F-inducible psoriasis-associated genes including DEFB4/hBD2, S100A7, CCL20, IL-8, and CHI3L1. Keratinocyte culture with recombinant IL-17F, siRNA knockdown of IκBζ, pharmacological inhibition of p38 MAPK and NF-κB, RT-PCR, Western blot, ELISA Experimental dermatology Medium 27576147
2018 IL-17F (but not IL-17A) suppression protects against chemically induced colitis in mice. Il17f-/- CD45RBhi CD4+ T cells induced milder colitis in Rag2-/- mice accompanied by increased intestinal Treg cells and expansion of Clostridium cluster XIVa (Treg-inducing microbiota) due to decreased expression of antimicrobial proteins. Anti-IL-17F antibody (but not anti-IL-17A antibody) suppressed colitis development. Il17f-/- mice, DSS colitis model, adoptive T cell transfer into Rag2-/- mice, anti-IL-17F neutralizing antibody treatment, 16S rRNA microbiota analysis, antimicrobial protein expression assays Nature immunology High 29915298
2009 IL-17A suppresses IL-17F production and secretion via IL-17RA signaling. In Il17a-/- mice, plasma IL-17F levels were elevated. Adding recombinant IL-17A to Il17a-/- splenocyte cultures reduced IL-17F mRNA and protein. This suppressive effect was absent in IL-17RA-deficient cells, demonstrating the IL-17RA requirement. Il17a-/- mice, plasma cytokine measurement (ELISA), ex vivo splenocyte culture with recombinant IL-17A, IL-17RA-deficient cells as controls, RT-PCR and ELISA for IL-17F Journal of immunology Medium 19542376
2020 Crystal structure of the extracellular domain of human IL-17RC in complex with IL-17F reveals that IL-17RC forms a symmetrical 2:1 complex with IL-17F (two IL-17RC molecules per IL-17F homodimer), competing with IL-17RA for cytokine binding. Biophysical studies show IL-17A and IL-17A/F heterodimer also form 2:1 complexes with IL-17RC, suggesting IL-17RA-independent IL-17 signaling pathways. X-ray crystallography of IL-17RC extracellular domain:IL-17F complex, biophysical binding assays (SPR/ITC) Immunity High 32187518
2017 IL-17F signals specifically through IL-17RC on epithelial cells and can exacerbate lower airway inflammation independently of IL-17RA. In Il17ra-/- mice, IL-17F/IL-17RC axis signaling significantly worsened Aspergillus/Pseudomonas lower airway infection and allergic airway inflammation. By contrast, in upper respiratory S. aureus infection, the IL-17F/IL-17RC axis was protective. Il17ra-/-, Il17a-/-, Il17f-/- knockout mice, airway infection models (Aspergillus, Pseudomonas, S. aureus), allergic airway inflammation model, comparison of receptor/ligand knockout phenotypes Cell reports High 28813677
2011 IL-17F deficiency significantly inhibits spontaneous intestinal tumorigenesis in the small intestine of ApcMin/+ mice. IL-17F ablation decreased IL-1β, Cox-2, and IL-17RC expression in tumors and reduced immune cell infiltration in lamina propria. IL-17A expression from CD4 T cells in lamina propria remained unchanged in the absence of IL-17F. IL-17F-deficient ApcMin/+ mice, tumor counting, immunohistochemistry, RT-PCR for IL-1β, Cox-2, IL-17RC Biochemical and biophysical research communications Medium 21939640
2011 MyD88-dependent TLR4 activation by LPS induces IL-17F production in mouse peritoneal macrophages, peaking at 12 h. C5a amplifies IL-17F production via C5aR through PI3K-Akt signaling (phosphorylation at Thr308 but not Ser473). Pharmacological inhibition of PI3K-Akt greatly reduced IL-17F production and mRNA. Full in vivo IL-17F production during endotoxemia and CLP sepsis requires C5a. MyD88-/- macrophages, LPS stimulation, recombinant C5a treatment, PI3K-Akt inhibitors, in vivo endotoxemia and CLP sepsis models, ELISA and RT-PCR FASEB journal Medium 21859896
2016 IL-17F-deficient mice are protected from hepatocellular damage in a methionine-choline deficient diet (MCDD)-induced NAFLD model, similar to IL-17A-/- and IL-17RA-/- mice, despite increased steatosis. Protection correlated with decreased hepatic T-cell and macrophage infiltration and decreased expression of inflammatory mediators. IL-17F-/-, IL-17A-/-, IL-17RA-/- knockout mice fed MCDD, liver histology, flow cytometry of hepatic immune cells, inflammatory mediator expression PloS one Medium 26895034
2016 IL-17F drives renal tissue injury in acute crescentic GN (nephrotoxic nephritis) through CD4+ T cell-derived IL-17F promoting neutrophil recruitment via induction of CXCL1 and CXCL5 in kidney cells. IL-17F-deficient nephritic mice had fewer renal infiltrating neutrophils; neutrophil depletion did not further affect GN in IL-17F-deficient mice. In chronic SLE (pristane) model, IL-17F-deficient mice developed less severe disease. IL-17F-/- mice, nephrotoxic nephritis model, IL-17F-neutralizing antibodies, adoptive transfer into Rag1-/- mice, neutrophil depletion, pristane-induced SLE model, CXCL1/CXCL5 induction assay in kidney cells Journal of the American Society of Nephrology High 27030744
2023 IL-17A and IL-17F are differentially regulated in psoriatic disease: their expression predominantly occurs in distinct T cell populations. STAT5/IL-2 signaling has opposing effects on each gene. Higher IL-17F expression is linked to greater cell proliferation. The IL17A-F locus carries a broad H3K4me3 region reflecting epigenetic plasticity. Single-cell RNA sequencing, novel cytokine-capture technique combined with ChIP-seq and RNA-seq, lesional skin tissue from psoriasis patients, in vitro culture systems with methylprednisolone treatment The Journal of allergy and clinical immunology Medium 37244461
2013 PGE2 and IL-23 plus IL-1β differentially regulate IL-17A and IL-17F in human Th17 memory cells: PGE2 induces IL-17A but not IL-17F via the EP4 receptor, promoting a switch from IL-17F to IL-17A predominant responses. IL-23 plus IL-1β preferentially induce IL-17F. The IL17A and IL17F loci have divergent epigenetic architectures in Th17 cells, with IL17A poised for preferential expression. Activated human peripheral CD4+ memory T cells and sorted Th17 memory cells, gene expression profiling, ChIP for histone marks, pharmacological EP4 receptor studies Cytokine Medium 23800789
2019 Fusobacterium nucleatum promotes intestinal inflammation in UC by targeting CARD3 through NOD2, which activates the IL-17F/NF-κB pathway in intestinal epithelial cells in vitro and in vivo. F. nucleatum infection of UC cell lines and mouse models in vivo, CARD3 knockdown/overexpression, NF-κB pathway reporters, IL-17F cytokine measurement by ELISA The Journal of pathology Medium 31610014
2015 IL-17A and IL-17F are both required for antimicrobial peptide production (mBD-3, CRAMP, mBD-14) and clearance of S. aureus nasal colonization in mice. Mice deficient in both IL-17A and IL-17F lost the ability to clear S. aureus; IL-17A alone was sufficient for nasal mBD-3 production ex vivo. IL-17A/IL-17F double-deficient mice, S. aureus nasal colonization model, ex vivo nasal tissue supernatant antimicrobial activity assay, antimicrobial peptide expression (RT-PCR, ELISA) Infection and immunity Medium 27736775
2019 In a TDI-induced steroid-insensitive asthma model, anti-IL-17F (but not anti-IL-17A) treatment ameliorated airway hyperresponsiveness and bronchial neutrophilia with decreased Th17 responses, while anti-IL-17A increased AHR and eosinophilia with amplified Th2 responses. Recombinant IL-17A and IL-17F showed opposite effects consistent with the antibody results, demonstrating distinct and opposing biological roles in this context. TDI-sensitized BALB/c mice, anti-IL-17A and anti-IL-17F monoclonal antibody treatment, recombinant IL-17A and IL-17F administration, airway hyperresponsiveness measurement, bronchoalveolar lavage cell counts, cytokine profiling The European respiratory journal Medium 30655284
2020 IL-17A and IL-17F enhance in vitro osteogenic differentiation and bone formation from human periosteal-derived cells (hPDCs). Dual neutralization of IL-17A and IL-17F by bimekizumab blocked T cell supernatant-induced and patient AS serum-induced in vitro bone formation more deeply than neutralization of either cytokine alone. Osteogenic blockade may involve increased expression of the Wnt antagonist DKK1. Human periosteal-derived cell osteogenic differentiation assay, recombinant IL-17A and IL-17F, T cell supernatants, AS patient serum, bimekizumab and monospecific antibody treatment, DKK1 expression assay RMD open Medium 32723833
2015 IL-17A and IL-17F induce autophagy in RAW 264.7 macrophages, as shown by LC3B-II accumulation, enhanced autophagic flux, increased autophagosome number/size, and acidic vesicular organelle formation. IL-17F was more efficient than IL-17A in promoting autophagy. IL-17F treatment significantly decreased intracellular counts of Mycobacterium terrae in macrophages. RAW 264.7 macrophage culture, recombinant IL-17A and IL-17F, LC3B-II Western blot, confocal microscopy of autophagosome formation, autophagic flux assay, intracellular M. terrae colony-forming unit counting Biomedicine & pharmacotherapy Medium 26796276

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Regulation of inflammatory responses by IL-17F. The Journal of experimental medicine 620 18411338
2008 IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice. The Journal of clinical investigation 351 19075395
2010 Expression of the T helper 17-associated cytokines IL-17A and IL-17F in asthma and COPD. Chest 310 20538817
2007 An IL-17F/A heterodimer protein is produced by mouse Th17 cells and induces airway neutrophil recruitment. Journal of immunology (Baltimore, Md. : 1950) 289 18025225
2008 Role of the novel Th17 cytokine IL-17F in inflammatory bowel disease (IBD): upregulated colonic IL-17F expression in active Crohn's disease and analysis of the IL17F p.His161Arg polymorphism in IBD. Inflammatory bowel diseases 280 18088064
1997 Melatonin receptor antagonists that differentiate between the human Mel1a and Mel1b recombinant subtypes are used to assess the pharmacological profile of the rabbit retina ML1 presynaptic heteroreceptor. Naunyn-Schmiedeberg's archives of pharmacology 275 9089668
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
2007 A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates inflammatory responses. Cell research 228 17452998
2007 Chromatin remodeling of interleukin-17 (IL-17)-IL-17F cytokine gene locus during inflammatory helper T cell differentiation. The Journal of biological chemistry 225 17218320
2006 IL-17F sequence variant (His161Arg) is associated with protection against asthma and antagonizes wild-type IL-17F activity. The Journal of allergy and clinical immunology 204 16630936
2005 TRP-ML1 regulates lysosomal pH and acidic lysosomal lipid hydrolytic activity. The Journal of biological chemistry 201 16361256
2011 Effects of interleukin (IL)-17A and IL-17F in human rheumatoid arthritis synoviocytes. Annals of the rheumatic diseases 159 21345813
2009 Genome-wide comparison between IL-17A- and IL-17F-induced effects in human rheumatoid arthritis synoviocytes. Journal of immunology (Baltimore, Md. : 1950) 142 19234208
2009 IL-17F: regulation, signaling and function in inflammation. Cytokine 141 19233684
2018 Suppression of IL-17F, but not of IL-17A, provides protection against colitis by inducing Treg cells through modification of the intestinal microbiota. Nature immunology 140 29915298
2016 Identification of IL-17F/frequent exacerbator endotype in asthma. The Journal of allergy and clinical immunology 128 27931975
2005 TRP-ML1 is a lysosomal monovalent cation channel that undergoes proteolytic cleavage. The Journal of biological chemistry 124 16257972
2010 IL-17RC is required for IL-17A- and IL-17F-dependent signaling and the pathogenesis of experimental autoimmune encephalomyelitis. Journal of immunology (Baltimore, Md. : 1950) 123 20231694
2012 Transcription of Il17 and Il17f is controlled by conserved noncoding sequence 2. Immunity 111 22244845
1992 Induction by bufalin of differentiation of human leukemia cells HL60, U937, and ML1 toward macrophage/monocyte-like cells and its potent synergistic effect on the differentiation of human leukemia cells in combination with other inducers. Cancer research 108 1324788
2010 Identification of cells expressing IL-17A and IL-17F in the lungs of patients with COPD. Chest 106 20864612
2016 Regulation of Inflammation by IL-17A and IL-17F Modulates Non-Alcoholic Fatty Liver Disease Pathogenesis. PloS one 102 26895034
2012 Association analysis of IL-17A and IL-17F polymorphisms in Chinese Han women with breast cancer. PloS one 89 22461912
2019 Fusobacterium nucleatum facilitates ulcerative colitis through activating IL-17F signaling to NF-κB via the upregulation of CARD3 expression. The Journal of pathology 84 31610014
2008 TRP-ML1 functions as a lysosomal NAADP-sensitive Ca2+ release channel in coronary arterial myocytes. Journal of cellular and molecular medicine 84 18754814
2012 Epithelial cell-derived IL-25, but not Th17 cell-derived IL-17 or IL-17F, is crucial for murine asthma. Journal of immunology (Baltimore, Md. : 1950) 81 22942422
2009 IL-17A controls IL-17F production and maintains blood neutrophil counts in mice. Journal of immunology (Baltimore, Md. : 1950) 81 19542376
2008 Membrane traffic and turnover in TRP-ML1-deficient cells: a revised model for mucolipidosis type IV pathogenesis. The Journal of experimental medicine 81 18504305
2023 The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases. Frontiers in immunology 79 37600764
2013 TH17 cell induction and effects of IL-17A and IL-17F blockade in experimental colitis. Inflammatory bowel diseases 77 23689808
2010 Involvement of IL-17F via the induction of IL-6 in psoriasis. Archives of dermatological research 75 20148256
2010 Association between IL-17F gene polymorphisms and susceptibility to and severity of rheumatoid arthritis (RA). Scandinavian journal of immunology 73 20618772
2016 Cytokines TNF-α, IL-6, IL-17F, and IL-4 Differentially Affect Osteogenic Differentiation of Human Adipose Stem Cells. Stem cells international 71 27667999
2008 Functional characterization of IL-17F as a selective neutrophil attractant in psoriasis. The Journal of investigative dermatology 66 18830271
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
2020 Interleukin (IL)-12 and IL-18 Synergize to Promote MAIT Cell IL-17A and IL-17F Production Independently of IL-23 Signaling. Frontiers in immunology 62 33329560
2015 Investigating the contribution of IL-17A and IL-17F to the host response during Escherichia coli mastitis. Veterinary research 61 26062913
2016 Interleukin-17A (IL-17A) and IL-17F Are Critical for Antimicrobial Peptide Production and Clearance of Staphylococcus aureus Nasal Colonization. Infection and immunity 60 27736775
2015 Nasal IL-17F is related to bronchial IL-17F/neutrophilia and exacerbations in stable atopic severe asthma. Allergy 59 25394579
2014 IL-17A, IL-17F and IL-23R Gene Polymorphisms in Polish Patients with Rheumatoid Arthritis. Archivum immunologiae et therapiae experimentalis 59 25387578
2019 Additive or Synergistic Interactions Between IL-17A or IL-17F and TNF or IL-1β Depend on the Cell Type. Frontiers in immunology 51 31396230
2020 Dual neutralisation of IL-17F and IL-17A with bimekizumab blocks inflammation-driven osteogenic differentiation of human periosteal cells. RMD open 47 32723833
2017 Ultra-Sensitive Measurement of IL-17A and IL-17F in Psoriasis Patient Serum and Skin. The AAPS journal 47 28534291
2016 IL-17F Promotes Tissue Injury in Autoimmune Kidney Diseases. Journal of the American Society of Nephrology : JASN 47 27030744
2005 Polymorphisms in the interleukin 17F gene (IL17F) and asthma. Genes and immunity 47 15703761
2016 Genetic polymorphisms of IL-17A, IL-17F, TLR4 and miR-146a in association with the risk of pulmonary tuberculosis. Scientific reports 46 27339100
2017 The IL-17F/IL-17RC Axis Promotes Respiratory Allergy in the Proximal Airways. Cell reports 45 28813677
2016 Role of IL-17A rs2275913 and IL-17F rs763780 polymorphisms in risk of cancer development: an updated meta-analysis. Scientific reports 45 26843459
2017 Neutralization of either IL-17A or IL-17F is sufficient to inhibit house dust mite induced allergic asthma in mice. Clinical science (London, England : 1979) 43 29026003
2019 IL-17F, rather than IL-17A, underlies airway inflammation in a steroid-insensitive toluene diisocyanate-induced asthma model. The European respiratory journal 42 30655284
2015 The polymorphism rs763780 in the IL-17F gene is associated with response to biological drugs in patients with psoriasis. Pharmacogenomics 42 26415694
2011 Reconstitution of lysosomal NAADP-TRP-ML1 signaling pathway and its function in TRP-ML1(-/-) cells. American journal of physiology. Cell physiology 42 21613607
1994 Cell cycle arrest and protein kinase modulating effect of bufalin on human leukemia ML1 cells. Anticancer research 42 8074471
2014 Potential involvement of IL-17F in asthma. Journal of immunology research 41 24829928
2014 Genetic variations of IL17F and IL23A show associations with Behçet's disease and Vogt-Koyanagi-Harada syndrome. Ophthalmology 40 25439430
2012 Chicken IL-17F: identification and comparative expression analysis in Eimeria-infected chickens. Developmental and comparative immunology 40 22922588
2020 IL-17A and IL-17F orchestrate macrophages to promote lung cancer. Cellular oncology (Dordrecht, Netherlands) 39 32227296
2011 IL-17F deficiency inhibits small intestinal tumorigenesis in ApcMin/+ mice. Biochemical and biophysical research communications 39 21939640
2007 The IL-17F signaling pathway is involved in the induction of IFN-gamma-inducible protein 10 in bronchial epithelial cells. The Journal of allergy and clinical immunology 39 17418381
2013 Association of IL-17A and IL-17F single nucleotide polymorphisms with susceptibility to osteoarthritis in a Korean population. Gene 38 24096234
2017 Association of IL17A and IL17F genes with rheumatoid arthritis disease and the impact of genetic polymorphisms on response to treatment. Immunology letters 37 28143790
2011 IL-17A and IL-17F expression in B lymphocytes. International archives of allergy and immunology 37 22123224
2011 Sensitivity of acute myeloid leukemia Kasumi-1 cells to binase toxic action depends on the expression of KIT and АML1-ETO oncogenes. Cell cycle (Georgetown, Tex.) 36 22101339
2009 Cutting edge: an IL-17F-CreEYFP reporter mouse allows fate mapping of Th17 cells. Journal of immunology (Baltimore, Md. : 1950) 36 19155467
2023 Differential regulation of IL-17A and IL-17F via STAT5 contributes to psoriatic disease. The Journal of allergy and clinical immunology 35 37244461
2012 Evaluation of IL17A expression and of IL17A, IL17F and IL23R gene polymorphisms in Brazilian individuals with periodontitis. Human immunology 35 23137879
2019 Bimekizumab: The First Dual Inhibitor of Interleukin (IL)-17A and IL-17F for the Treatment of Psoriatic Disease and Ankylosing Spondylitis. BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 34 31172372
2014 Significant association between IL23R and IL17F polymorphisms and clinical features of colorectal cancer. Immunology letters 33 24440568
2017 IL-17F regulates psoriasis-associated genes through IκBζ. Experimental dermatology 32 27576147
2016 IL17A and IL17F gene polymorphisms in patients with rheumatoid arthritis. BMC musculoskeletal disorders 32 27169372
2015 IL-17A and IL-17F induce autophagy in RAW 264.7 macrophages. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 32 26796276
2009 IL-17F-induced IL-11 release in bronchial epithelial cells via MSK1-CREB pathway. American journal of physiology. Lung cellular and molecular physiology 32 19251839
2014 Expression of IL-17A and IL-17F in lipopolysaccharide-induced acute lung injury and the counteraction of anisodamine or methylprednisolone. Cytokine 31 24548428
2013 Regulatory effects of C5a on IL-17A, IL-17F, and IL-23. Frontiers in immunology 31 23316190
2020 Presence, function, and regulation of IL-17F-expressing human CD4+ T cells. European journal of immunology 30 31850514
2011 MyD88-dependent production of IL-17F is modulated by the anaphylatoxin C5a via the Akt signaling pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 29 21859896
2014 IL-15 and IL-17F are differentially regulated and expressed in mycosis fungoides (MF). Cell cycle (Georgetown, Tex.) 27 24621498
2014 IL-17F gene polymorphism is associated with susceptibility to acute myeloid leukemia. Journal of cancer research and clinical oncology 27 24793548
2021 Influence of IL10 (rs1800896) Polymorphism and TNF-α, IL-10, IL-17A, and IL-17F Serum Levels in Ankylosing Spondylitis. Frontiers in immunology 26 34290697
2017 Interleukin (IL)-23 Receptor, IL-17A and IL-17F Gene Polymorphisms in Brazilian Patients with Rheumatoid Arthritis. Archivum immunologiae et therapiae experimentalis 26 28547498
2020 Myeloid-Derived Suppressor Cell-Derived Arginase-1 Oppositely Modulates IL-17A and IL-17F Through the ESR/STAT3 Pathway During Colitis in Mice. Frontiers in immunology 24 32391010
2013 The IL17A and IL17F loci have divergent histone modifications and are differentially regulated by prostaglandin E2 in Th17 cells. Cytokine 23 23800789
2017 Expression of mRNA IL-17F and sIL-17F in atopic asthma patients. BMC research notes 22 28606156
2018 Expression of IL-17F is associated with non-pathogenic Th17 cells. Journal of molecular medicine (Berlin, Germany) 21 29959474
2014 Clinical significance of IL-23 regulating IL-17A and/or IL-17F positive Th17 cells in chronic periodontitis. Mediators of inflammation 21 25525302
2013 Combined blockade of IL-17A and IL-17F may prevent the development of experimental colitis. Immunotherapy 21 23998727
2012 The IL6 gene polymorphism -634C>G and IL17F gene polymorphism 7488T>C influence bone mineral density in young and elderly Japanese women. Gene 21 22579472
2019 Preliminary Report on Interleukin-22, GM-CSF, and IL-17F in the Pathogenesis of Acute Anterior Uveitis. Ocular immunology and inflammation 20 31763950
2018 Levels of IL-17F and IL-33 correlate with HLA-DR activation in clinical-grade human bone marrow-derived multipotent mesenchymal stromal cell expansion cultures. Cytotherapy 20 30447901
2012 Association between polymorphisms in IL17F and male asthma in a Chinese population. Journal of investigational allergology & clinical immunology 20 22812194
2012 Association of genetic polymorphisms in IL17A and IL17F with gastro-duodenal diseases. Journal of gastrointestinal and liver diseases : JGLD 20 23012664
2022 Inhibiting IL-17A and IL-17F in Rheumatic Disease: Therapeutics Help to Elucidate Disease Mechanisms. Current rheumatology reports 19 35861937
2015 IL-17A and IL-17F polymorphisms in rheumatoid arthritis and Sjögren's syndrome. Clinical oral investigations 19 26232893
2015 Association of IL-17A and IL-17F gene polymorphisms with chronic hepatitis B and hepatitis B virus-related liver cirrhosis in a Chinese population: A case-control study. Clinics and research in hepatology and gastroenterology 19 26546176
2008 IL-17F/IL-17R interaction stimulates granulopoiesis in mice. Experimental hematology 19 18723265
2018 Inflammatory Dietary Pattern, IL-17F Genetic Variant, and the Risk of Colorectal Cancer. Nutrients 18 29874787
2016 Association between IL17A and IL17F polymorphisms and risk of Henoch-Schonlein purpura in Chinese children. Rheumatology international 18 27021337
2015 Serum IL-17F combined with VEGF as potential diagnostic biomarkers for oral squamous cell carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 18 25613064
2015 Involvement of IL17A, IL17F and IL23R Polymorphisms in Colorectal Cancer Therapy. PloS one 18 26083022
2013 Intracellular two-phase Ca2+ release and apoptosis controlled by TRP-ML1 channel activity in coronary arterial myocytes. American journal of physiology. Cell physiology 18 23283937

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