Affinage

IL17C

Interleukin-17C · UniProt Q9P0M4

Length
197 aa
Mass
21.8 kDa
Annotated
2026-06-10
62 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL-17C is an epithelial-derived cytokine that drives innate and adaptive inflammatory responses by signaling through a heterodimeric IL-17RA/IL-17RE receptor complex preferentially expressed on tissue epithelial cells, acting in an autocrine/paracrine fashion to induce proinflammatory cytokines, chemokines, and antimicrobial peptides (PMID:21993848, PMID:21993849). Functionally distinct from IL-17A, it was originally identified as a cytokine that stimulates TNF-α and IL-1β release from monocytic cells and does not bind the IL-17A receptor (PMID:10639155). At barrier surfaces it is induced by bacterial and viral pathogens through pattern-recognition and NF-κB signaling — NOD2 in keratinocytes responding to S. aureus (PMID:23892590), TLR3-TRIF-NF-κB and TLR2/4/5 routes in airway and intestinal epithelium (PMID:23944933, PMID:28346430), and NF-κB/p38 MAPK during viral-bacterial coinfection (PMID:30504421) — and reinforces epithelial defense by inducing antimicrobial peptides and maintaining tight-junction proteins such as occludin (PMID:23024280, PMID:31221216). IL-17C participates in self-amplifying inflammatory loops: it is upregulated by Th17 cytokines (TNF-α, IL-17A, IL-22) acting via NF-κB and AP-1/p38 (PMID:36130829), reciprocally sustained by IL-36γ (PMID:25299544, PMID:36496195), and negatively regulated by MCPIP1/Regnase-1 (PMID:27920272) and by IL-13/STAT6 signaling that reduces NF-κB p65 binding to the IL-17C promoter (PMID:29203240). Through IL-17RE on CD4+ TH17 cells it amplifies adaptive TH17-driven tissue injury (PMID:29483158), and its downstream effects span neutrophil recruitment via CXCL1/KC/MIP-2 (PMID:27694471, PMID:30504421), M1 macrophage polarization through STAT1 (PMID:39568050), and tumor angiogenesis via a STAT3/miR-23a-3p/SEMA6D axis (PMID:32492770). These activities give IL-17C dual protective and pathogenic roles across infection, psoriasis, colitis, nephropathy, and cancer (PMID:21993849, PMID:23359500, PMID:32331702), making it a therapeutic target addressed by neutralizing antibodies (PMID:29474945, PMID:31793105).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2000 Medium

    Established IL-17C as a distinct cytokine by showing it induces TNF-α and IL-1β from monocytic cells yet, unlike IL-17A, does not bind the IL-17 receptor or induce fibroblast IL-6.

    Evidence Recombinant protein cytokine-release assays, FACS binding, and IL-17 receptor binding assays in cell lines

    PMID:10639155

    Open questions at the time
    • Did not identify the functional receptor
    • Cellular source and physiological context unaddressed
  2. 2011 High

    Defined the IL-17C receptor as the IL-17RA/IL-17RE heterodimer on epithelial cells, answering how IL-17C signals and revealing an autocrine epithelial innate-immune function with context-dependent protective and pathogenic roles.

    Evidence Receptor binding and co-IP, IL-17RE-deficient mice, imiquimod skin and DSS colitis and C. rodentium infection models

    PMID:21993848 PMID:21993849

    Open questions at the time
    • Structural basis of receptor engagement not resolved
    • Downstream signaling components downstream of IL-17RE not fully mapped
  3. 2012 High

    Showed IL-17C maintains epithelial barrier integrity by directly regulating the tight-junction protein occludin, linking it to protection in acute colitis.

    Evidence IL-17C-deficient mice in DSS colitis with tight-junction protein assessment

    PMID:23024280

    Open questions at the time
    • Direct mechanism of occludin regulation not defined
    • Relationship between barrier and inflammatory functions unresolved
  4. 2013 High

    Identified pathogen-sensing routes (NOD2, TLR3/5) that induce epithelial IL-17C and demonstrated its requirement for antibacterial defense and for driving psoriasiform skin inflammation.

    Evidence NOD2 promoter reporter and variant analysis, siRNA knockdown with S. aureus survival, keratinocyte-specific transgenic overexpression, HBEC infection

    PMID:23221046 PMID:23359500 PMID:23892590

    Open questions at the time
    • Relative contribution of distinct PRR pathways across tissues unclear
    • Why the same cytokine is protective vs pathogenic not mechanistically resolved
  5. 2014 High

    Mapped upstream induction and amplification of IL-17C, showing NF-κB-driven transcription via TLR3-TRIF, Th17-cytokine amplification, and IL-36γ reciprocal loops, and CCL20-mediated TH17 chemoattraction.

    Evidence Primary NHBE/IEC/keratinocyte stimulation with siRNA, pathway inhibitors, ELISA, patient tissue immunohistochemistry

    PMID:23944933 PMID:25299544 PMID:25492478

    Open questions at the time
    • Quantitative hierarchy among inducers not established
    • In vivo relevance of the IL-36γ loop incompletely defined
  6. 2015 Medium

    Demonstrated a pathogenic role for IL-17C in lethal systemic Candida infection through direct action on renal epithelial cells, dissociating immunopathology from fungal clearance.

    Evidence IL-17C-deficient mice in systemic fungal infection with in vitro renal epithelial stimulation

    PMID:26166766

    Open questions at the time
    • Receptor dependence in this model not directly tested
    • Specific renal cell mediators not identified
  7. 2016 High

    Defined negative regulation by MCPIP1/Regnase-1 and showed IL-17C amplifies neutrophilic chemokine responses during bacterial pneumonia and TH17-driven hepatitis.

    Evidence Zc3h12a/Il17c epistasis double knockouts, bone marrow chimeras, IL-17C-/- and IL-17A-/- pneumonia models, Con A hepatitis models

    PMID:27694471 PMID:27920272 PMID:27956525

    Open questions at the time
    • Molecular target of MCPIP1 within the IL-17C axis not specified
    • Tissue-specific balance of regulators unclear
  8. 2017 Medium

    Extended IL-17C signaling beyond epithelium to neurons and tumor settings, showing IL-17RE on sensory neurons mediates neurite guidance and IL-17C promotes tumor-associated neutrophil recruitment.

    Evidence Microfluidic neurite assays, neuron apoptosis assays, IL-17C-/- and TLR2/4-/- metastatic lung cancer models, immunostaining

    PMID:28346430 PMID:28663436

    Open questions at the time
    • Neuronal signaling downstream of IL-17RE undefined
    • Direct vs indirect tumor-promoting mechanisms not separated
  9. 2018 High

    Showed IL-17RE on CD4+ TH17 cells directly amplifies adaptive TH17 responses and established IL-17C neutralization (MOR106) as therapeutically effective in skin inflammation models.

    Evidence IL-17C-/- and IL-17RE-/- glomerulonephritis/lupus models, bone marrow chimeras, neutralizing antibody in psoriasis and AD models

    PMID:29474945 PMID:29483158

    Open questions at the time
    • Intracellular signaling in TH17 cells downstream of IL-17RE not mapped
    • Durability and specificity of antibody effects in humans not addressed
  10. 2017 High

    Identified IL-13/STAT6 as a negative regulator that suppresses NF-κB p65 binding to the IL-17C promoter without affecting upstream NF-κB activation.

    Evidence ChIP of IL-17C promoter, p65/STAT6 siRNA, JAK inhibition in primary NHBE cells

    PMID:29203240

    Open questions at the time
    • Mechanism by which STAT6 blocks p65 recruitment not defined
    • In vivo relevance in Th2 disease not established
  11. 2020 High

    Consolidated IL-17C as a pathogenic driver in kidney injury and uncovered effector mechanisms including STAT3/miR-23a-3p/SEMA6D-driven tumor angiogenesis and directional basolateral epithelial secretion.

    Evidence IL-17RE-/- mice, neutralizing antibody, siRNA in tubular cells, kidney IRI models, CRC xenograft angiogenesis assays, air-liquid interface HBE cultures

    PMID:31793105 PMID:32232015 PMID:32331702 PMID:32492770

    Open questions at the time
    • Receptor-proximal signaling driving STAT3 activation not defined
    • Determinants of polarized secretion unknown
  12. 2023 Medium

    Detailed NF-κB as the predominant transcriptional driver of hypoxia/high-glucose-induced renal IL-17C and validated delayed IL-17C neutralization as reno-protective across IRI and diabetic nephropathy.

    Evidence ALDH2-/- mice, HK-2 hypoxia model, NF-κB and HIF-1α inhibitors, p65 siRNA, neutralizing antibody in IRI and db/db models

    PMID:36865346 PMID:37263138

    Open questions at the time
    • Link between ALDH2 deficiency and NF-κB activation incompletely defined
    • Translational therapeutic window in human kidney disease unknown
  13. 2024 High

    Expanded the cellular targets of IL-17C to macrophages, showing STAT1-driven M1 polarization via IL-17RE, and demonstrated direct epithelial damage in human Fallopian tube during gonococcal infection.

    Evidence IL-17c-/- asthma model, IL-17RE-overexpressing macrophages with STAT1/STAT6 analysis, human Fallopian tube explants with N. gonorrhoeae and purified IL-17C, RNA-seq

    PMID:38704381 PMID:39568050

    Open questions at the time
    • How a single receptor produces distinct STAT1 vs STAT3 outputs unresolved
    • Mechanism of IL-17C-induced epithelial sloughing undefined
  14. 2025 Medium

    Identified intracellular effector consequences of IL-17C signaling, including SMURF2 upregulation driving PPP6C ubiquitination in keratinocytes and YAP/CCN2- and PI3K/AKT/mTOR-linked induction and effects in macrophage/chondrocyte contexts.

    Evidence Co-IP, ubiquitination assays, siRNA/overexpression in HaCaT and imiquimod psoriasis; macrophage RhoA conditional knockout with transcriptomics in OA model

    PMID:40244332 PMID:41620554

    Open questions at the time
    • Single Co-IP for SMURF2-PPP6C without reciprocal/structural validation
    • How IL-17C links receptor engagement to SMURF2 transcription unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The receptor-proximal signaling cascade that converts IL-17RA/IL-17RE engagement into distinct outputs (STAT1 vs STAT3 vs NF-κB) and the structural basis of ligand-receptor recognition remain unresolved.
  • No structural model of the IL-17C/IL-17RA/IL-17RE complex
  • Adaptor and kinase intermediates downstream of IL-17RE not defined
  • Determinants of protective vs pathogenic outcomes not mechanistically explained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3
Partners
IL17RAIL17RE

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 IL-17C was cloned and shown to stimulate release of TNF-α and IL-1β from the monocytic cell line THP-1, and to bind THP-1 cells by FACS analysis. IL-17C does not bind the human IL-17 receptor extracellular domain and does not induce IL-6 from fibroblasts, distinguishing it from IL-17A. Recombinant protein expression, cytokine release assay (ELISA), FACS binding assay, IL-17 receptor binding assay Proceedings of the National Academy of Sciences of the United States of America Medium 10639155
2011 IL-17C signals through a heterodimeric receptor complex composed of IL-17RA and IL-17RE, which is preferentially expressed on tissue epithelial cells. IL-17C acts in an autocrine manner on epithelial cells to stimulate proinflammatory cytokines, chemokines, and antimicrobial peptides. IL-17C promoted inflammation in imiquimod-induced skin inflammation but exerted protective functions in DSS-induced colitis. Receptor binding assays, gene expression analysis, knockout mouse models (imiquimod and DSS colitis models), co-immunoprecipitation of receptor complex Nature immunology High 21993848
2011 IL-17RE is the specific functional receptor for IL-17C. IL-17C signals through the IL-17RE–IL-17RA heterodimeric complex to induce antibacterial peptides and proinflammatory molecules in colon epithelial cells. IL-17C is upregulated in colon epithelial cells during Citrobacter rodentium infection, acts synergistically with IL-22 to induce antibacterial peptides, and loss of IL-17RE leads to greater bacterial burden and early mortality. Receptor identification (IL-17RE as orphan receptor for IL-17C), IL-17RE-deficient mouse model, infection model with C. rodentium, gene expression assays Nature immunology High 21993849
2012 IL-17C is required for regulation of acute experimental colitis (DSS model); IL-17C-deficient mice show exacerbated disease with increased IL-17 expression by γδ T cells and Th17 cells. IL-17C directly regulates the expression of the tight junction molecule occludin by colonic epithelial cells. IL-17C-deficient mouse model, DSS colitis model, gene expression analysis, tight junction protein assessment Journal of immunology High 23024280
2013 NOD2 activation in keratinocytes mediates Staphylococcus aureus-induced IL-17C expression via the first NF-κB binding site in the IL-17C promoter. Crohn's disease-associated NOD2 mutations (3020insC, R702W) significantly reduced NOD2-mediated IL-17C induction. IL-17C knockdown increased S. aureus survival in keratinocytes. NOD2 overexpression in HEK293 cells, IL-17C promoter reporter assay, siRNA knockdown, S. aureus infection of primary keratinocytes The Journal of investigative dermatology High 23892590
2013 Keratinocyte overexpression of IL-17C drives psoriasiform skin inflammation in mice; involved skin shows epidermal hyperplasia, angiogenesis, leukocyte infiltration, and upregulation of TNF-α, IL-1α/β, IL-17A/F, IL-23p19. IL-17C and TNF-α together produce similar inflammatory gene responses in keratinocytes as IL-17A/TNF-α, indicating a positive proinflammatory feedback loop. TNF-α inhibition ameliorated the phenotype. Transgenic mouse model (keratinocyte-specific IL-17C overexpression), cytokine stimulation of primary keratinocytes, TNF-α inhibitor treatment Journal of immunology High 23359500
2013 IL-17C is expressed by human bronchial epithelial cells (HBECs) in response to bacterial pathogens (Pseudomonas aeruginosa, Haemophilus influenzae) and TLR3/TLR5 ligands. IL-17C enhanced inflammatory responses of respiratory epithelial cells; cigarette smoke suppressed IL-17C expression in response to bacterial infection. In vitro bacterial infection of HBECs, TLR ligand stimulation, gene expression analysis, in vivo mouse colonization model American journal of respiratory cell and molecular biology Medium 23221046
2014 In human IBD, IL-17C production in intestinal epithelial cells is regulated by TNF-α through NF-κB, ERK1/2, and p38 pathways, and by IL-17A through Akt, MCPIP1 (Regnase-1), and C/EBPδ pathways. IL-17A strongly amplifies TNF-α-induced IL-17C production in enteroendocrine and goblet cells. IL-17C upregulates the Th17 chemoattractant CCL20 in IECs. Primary IEC stimulation, signaling pathway inhibitors, qPCR, immunoblotting, ELISA, immunohistochemistry of IBD patient tissue Mucosal immunology Medium 25492478
2014 IL-17C expression in airway bronchial epithelial cells is induced by polyI:C via the TLR3–TRIF–NF-κB pathway. IL-17C acts in an autocrine/paracrine manner through IL-17RE to enhance expression of antimicrobial peptides (hBD2) and proinflammatory mediators (CSF3, S100A12). Knockdown of IL-17RE attenuated polyI:C-induced hBD2, CSF3, and S100A12 expression without reducing IL-17C itself. Primary normal human bronchial epithelial (NHBE) cell stimulation, pathway inhibitors (Pepinh-TRIF, BAY11, NF-κB p65 siRNA), IL-17RE siRNA knockdown, IL-17C siRNA knockdown American journal of respiratory cell and molecular biology High 23944933
2014 IL-36γ induces IL-17C expression in keratinocytes and IL-17C reciprocally sustains a proinflammatory self-amplifying loop with IL-36γ. IL-17C affects keratinocyte defensin gene expression only in combination with TNF-α (not alone). Both IL-36γ and IL-17C are elevated in anti-TNF-induced psoriasiform skin lesions of Crohn's disease patients and their expression levels are strongly correlated. Primary keratinocyte stimulation, qRT-PCR, immunoblotting, ELISA, immunohistochemistry of patient skin biopsies Inflammatory bowel diseases Medium 25299544
2015 IL-17C is required for lethal inflammation during systemic fungal (Candida) infection; IL-17C-deficient mice show increased survival and attenuated kidney tissue damage with decreased pro-inflammatory cytokine expression despite similar fungal loads. IL-17C directly acts on renal epithelial cells in vitro to promote pro-inflammatory cytokine production. IL-17C-deficient mouse model, systemic fungal infection model, in vitro renal epithelial cell stimulation, cytokine measurement Cellular & molecular immunology Medium 26166766
2016 MCPIP1 (Regnase-1) is a negative regulator of IL-17C signaling in non-hematopoietic (epithelial) cells. MCPIP1-deficient keratinocytes show increased responsiveness to IL-17A and IL-17C stimulation. Epistasis analysis (Zc3h12a+/-Il17c-/- double mice) demonstrated that pathology in MCPIP1-deficient mice is partly dependent on IL-17C. MCPIP1 (Zc3h12a) heterozygous knockout mice, radiation bone marrow chimeras, double-knockout epistasis (Zc3h12a+/-Il17c-/-), primary keratinocyte stimulation with IL-17C Journal of immunology High 27920272
2016 IL-17A-mediated upregulation of epithelial IL-17C amplifies chemokine (KC, MIP-2) production and neutrophil recruitment in acute P. aeruginosa pneumonia. IL-17C-deficient mice show decreased neutrophil numbers and chemokine expression. IL-17A stimulation of primary alveolar epithelial cells directly increases IL-17C expression in vitro. IL-17C-/- and IL-17A-/- mouse models, P. aeruginosa lung infection model, primary alveolar epithelial cell stimulation, cytokine/chemokine measurement American journal of physiology. Lung cellular and molecular physiology Medium 27694471
2016 IL-17C/IL-17RE axis promotes TH17 cell-driven autoimmune hepatitis. IL-17C is produced by hepatocytes, and IL-17RE is expressed on liver-resident T cells. Mechanistically, IL-17C augments IL-2 expression by intrahepatic CD4+ T cells to promote NK cell activation and liver damage. IL-17C and IL-17RE knockout mouse models (Con A hepatitis model), human patient liver samples, in vitro T cell stimulation, cytokine measurement Journal of immunology Medium 27956525
2017 IL-17C expression in airway epithelial cells is induced by NTHi (nontypeable Haemophilus influenzae) through TLR-2/4 signaling. IL-17C promotes neutrophil recruitment into tumors by increasing neutrophil chemokine (KC, MIP-2) expression in lung cancer cells, thereby enhancing tumor growth in a metastatic model. IL-17C-/- and TLR-2/4-/- mouse models, metastatic lung cancer model with NTHi, in vitro cytokine stimulation of lung cancer cells, neutrophil chemokine measurement Oncogene Medium 28346430
2017 Keratinocytes produce IL-17C during HSV-2 reactivation. IL-17RE (the IL-17C-specific receptor) is expressed on nerve fibers in human skin and sensory neurons in dorsal root ganglia. Exogenous IL-17C provided directional guidance and promoted neurite growth and branching in microfluidic devices, and IL-17C pretreatment reduced apoptosis in HSV-2-infected primary neurons. Human skin biopsy analysis, ex vivo microfluidic neurite growth assay, primary neuron apoptosis assay with recombinant IL-17C, immunostaining of human skin and DRG The Journal of experimental medicine Medium 28663436
2017 IL-13 negatively regulates IL-1β-induced IL-17C expression in airway epithelial cells by suppressing NF-κB-mediated transcriptional activation. IL-1β induces IL-17C through NF-κB (p65 binds IL-17C promoter at -130/-120 and -157/-147 sites); IL-13 activates JAK/STAT6 signaling to reduce p65 binding to the IL-17C promoter without affecting upstream IκBα/NF-κB activation. Primary NHBE cell stimulation, NF-κB p65 siRNA, STAT6 siRNA, JAK inhibitor (ruxolitinib), chromatin immunoprecipitation (ChIP) of IL-17C promoter, Western blot Biochemical and biophysical research communications High 29203240
2018 IL-17C/IL-17RE signaling on CD4+ TH17 cells promotes TH17-driven glomerular inflammation. IL-17RE is highly expressed by CD4+ TH17 cells; loss of IL-17RE specifically prevents TH17 responses and subsequent tissue injury. Bone marrow transplantation experiments showed IL-17C is produced by tissue-resident (non-lymphocyte) cells. IL-17C-/- and IL-17RE-/- mouse models of crescentic GN and lupus nephritis, bone marrow transplantation chimeras, TH17 response assessment, human patient serum IL-17C measurement Journal of the American Society of Nephrology High 29483158
2018 Anti-IL-17C antibody MOR106 selectively binds human and mouse IL-17C and inhibits IL-17C binding to its IL-17RE receptor. MOR106 suppressed skin inflammation in IL-23-induced psoriatic and calcipotriol-induced AD mouse models, reducing T cells, neutrophils, eosinophils, TSLP, IL-33, IgE, and mast cell numbers. Neutralizing antibody generation and characterization, in vivo IL-23-induced psoriasis model, calcipotriol AD model, flaky tail mouse model, cytokine/immune cell measurements The Journal of investigative dermatology Medium 29474945
2018 HRV-bacterial coinfection synergistically induces IL-17C expression in bronchial epithelial cells via NF-κB and p38 MAPK signaling. IL-17C induces CXCL1 release from epithelial cells, and IL-17C knockdown significantly reduces CXCL1 induction and neutrophil chemotaxis. Primary bronchial epithelial cell infection with HRV and bacteria, pharmacological inhibitors (NF-κB, p38 MAPK), IL-17C siRNA knockdown, CXCL1 ELISA, neutrophil chemotaxis assay Journal of immunology Medium 30504421
2019 TLR5 signaling mediates F4+ ETEC-induced IL-17C expression in porcine intestinal epithelial cells. Both ETEC infection and exogenous IL-17C increased expression of antimicrobial peptides (pBD-2) and tight junction proteins (claudin-1, claudin-2, occludin), demonstrating an autocrine/paracrine epithelial defense function. Porcine IPEC-J2 cell infection model, TLR5 signaling analysis, recombinant IL-17C stimulation, gene expression assay Veterinary research Medium 31221216
2019 IL-17C/IL-17RE axis promotes neutrophil recruitment during acute S. pneumoniae pneumonia. IL-17RE-deficient mice showed decreased pulmonary neutrophil numbers, decreased G-CSF and TNF-α, and reduced granulocyte-monocyte progenitor (GMP) fractions. IL-17C-deficient mice also showed reduced neutrophil numbers at 24h post-infection. IL-17RE-/- and IL-17C-/- mouse models, S. pneumoniae lung infection, flow cytometry of immune cells and bone marrow progenitors, cytokine measurement Infection and immunity Medium 31481409
2020 Replication-dependent rhinovirus infection drives basolateral (but not apical) IL-17C protein release from differentiated airway epithelial cells. Columnar epithelial cells express more IL-17C than basal cells. Basolateral IL-17C acts in an autocrine/paracrine manner to promote basolateral CXCL1 production. Highly differentiated human bronchial epithelial (HBE) cell air-liquid interface cultures, apical HRV infection, viral replication inhibitor, separated apical/basolateral secretion analysis, enriched cell population analysis Frontiers in cellular and infection microbiology Medium 32232015
2020 IL-17C has a pathogenic role in kidney ischemia/reperfusion injury. IL-17C is upregulated in hypoxic kidney tubular epithelial cells. Neutralizing IL-17C antibody or IL-17RE knockout attenuated tubular injury, oxidative stress, inflammation, TH17 activation, IL-17A expression, and downstream TNF-α and IL-1β. IL-17C knockdown with siRNA decreased hypoxia-induced inflammation in kidney tubular cells, and silencing IL-17RE abrogated IL-17C effects. IL-17RE-/- mouse model, neutralizing antibody treatment, siRNA knockdown in kidney tubular cells, kidney IRI model, cytokine and oxidative stress measurements Kidney international High 32331702
2020 IL-17C promotes tumor angiogenesis in colorectal cancer by inducing VEGF production via a STAT3/miR-23a-3p/SEMA6D axis. IL-17C activates STAT3 to increase miR-23a-3p expression, which suppresses SEMA6D to permit VEGF production. IL-17C-induced angiogenesis was blocked by VEGFR2 inhibitor Ki8751 in xenograft experiments. In vitro angiogenesis assay, mouse xenograft model, ELISA, siRNA gene silencing, VEGFR2 inhibitor treatment, immunostaining Cells Medium 32492770
2020 IL-17C amplifies epithelial inflammation through autocrine induction of IL-17C itself in keratinocytes, and promotes expression of innate cytokines, antimicrobial peptides (IL-36G, S100A7, HBD2) and chemokines (CXCL8, CXCL10, CCL5, VEGF). IL-17C depletion with anti-IL-17C antibody MOR106 significantly reduced T cells, neutrophils, and eosinophils in mouse psoriasis and AD models and downregulated inflammatory mediators in human skin explants. Primary human keratinocyte stimulation, neutralizing antibody MOR106, IL-23 psoriasis and MC903 AD mouse models, flow cytometry, human skin ex vivo explant cultures, neutrophil migration assay Journal of the European Academy of Dermatology and Venereology Medium 31793105
2022 Th17-derived cytokines TNF-α, IL-17A, and IL-22 synergistically enhance IL-17C expression in colonic epithelial cells. TNF-α acts through NF-κB (blocked by IκBα inhibitor), while IL-17A and IL-22 act through AP-1 in a p38 MAPK-dependent manner to amplify IL-17C expression, establishing an inflammatory amplification loop between epithelial cells and Th17 cells. Human colonic epithelial cell lines and primary colonic organoids, cytokine stimulation, pharmacological NF-κB and p38 MAPK inhibitors, qPCR Journal of immunology Medium 36130829
2022 LL37 activates TLR8 in keratinocytes and induces IL-17C through the induction of IL-36γ. IL-36 receptor antagonistic antibody suppressed IL-17C induced by LL37, placing IL-36γ upstream of IL-17C induction in this pathway. IL-17C was not altered by blockade of TLR7/8 directly, indicating LL37 acts on IL-17C indirectly through IL-36γ. Primary keratinocyte stimulation with LL37, TLR7/8 inhibitors, IL-36 receptor antagonist antibody, psoriatic skin immunostaining, gene expression analysis The Journal of investigative dermatology Medium 36496195
2023 Hypoxia-induced IL-17C upregulation in kidney tubular cells is predominantly mediated by the NF-κB pathway (IκBα/NF-κB p65 phosphorylation). ALDH2 deficiency increases NF-κB phosphorylation, leading to increased IL-17C expression during kidney IRI. NF-κB inhibition in HK-2 cells prevented the ALDH2-knockdown-induced increase in IL-17C. ALDH2-/- mouse model, kidney IRI, RNA-seq, PCR, Western blot, HK-2 cell hypoxia/reoxygenation model, ALDH2 siRNA knockdown, NF-κB inhibitor Oxidative medicine and cellular longevity Medium 36865346
2023 Delayed (post-ischemia) IL-17C neutralization has reno-protective effects on kidney IRI. IL-17C blockade attenuated diabetic nephropathy (DN), including albuminuria, mesangial matrix accumulation, and podocyte loss. Mechanistic studies showed that hypoxia or high glucose-induced IL-17C upregulation is predominantly mediated by the NF-κB pathway, and IL-17C neutralization repressed downstream pro-inflammatory cytokines and Th17/IL-17A activation. IL-17C neutralizing antibody treatment in mouse IRI and db/db diabetic nephropathy models, NF-κB p65 siRNA knockdown, HIF-1α inhibitor (YC-1), kidney function/histology assessment, cytokine measurement EBioMedicine Medium 37263138
2024 IL-17C is highly induced in human Fallopian tube epithelium during N. gonorrhoeae infection. Human Fallopian tubes express the IL-17C receptor on the epithelial surface. Treatment of Fallopian tube explants with purified IL-17C induces pro-inflammatory cytokine secretion and causes sloughing of the epithelium and generalized tissue damage. Human Fallopian tube ex vivo culture with N. gonorrhoeae, RNA sequencing, purified IL-17C treatment, receptor expression analysis, histological assessment Nature communications High 38704381
2024 IL-17C promotes M1 macrophage polarization in neutrophilic asthma via IL-17RE. In vitro, IL-17C synergizes with IFN-γ to activate STAT1 in IL-17RE-overexpressing macrophages (Raw264.7), upregulating M1-related genes, while inhibiting IL-4-induced STAT6 activation and M2 differentiation. In vivo, deficiency of IL-17C reversed pro-inflammatory phenotypes and inhibited M1 macrophage expansion. IL-17c-/- mouse model, OVA/CFA asthma model, exogenous rmIL-17C administration, IL-17RE-overexpressing Raw264.7 cells, flow cytometry, Western blot for STAT1/STAT6 Cell communication and signaling Medium 39568050
2025 IL-17C upregulates SMURF2 expression in keratinocytes, leading to psoriasis-like changes. SMURF2 interacts with PPP6C (by co-immunoprecipitation) and promotes its ubiquitination and degradation. Silencing SMURF2 inhibited the effects of IL-17C on keratinocytes, and SMURF2 overexpression enhanced IL-17C effects by targeting PPP6C for degradation. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown of SMURF2, lentiviral overexpression, imiquimod psoriasis mouse model, HaCaT cell stimulation with IL-17C, Western blot, flow cytometry Cell biology international Medium 40244332
2026 Macrophage RhoA ablation leads to activation of Hippo pathway effectors YAP/CCN2, causing IL-17C transcription independently of the canonical ROCK pathway. IL-17C secreted by RhoA-deficient macrophages induces chondrocyte senescence (increased p53/p21, ROS, mitochondrial dysfunction, suppressed autophagy) via activation of the PI3K/AKT/mTOR pathway. Macrophage-specific RhoA conditional knockout mouse model, OA mouse model, transcriptome sequencing, Western blot, immunofluorescence, ELISA, YAP/CCN2 pathway analysis Cell biology and toxicology Medium 41620554

Source papers

Stage 0 corpus · 62 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 IL-17C regulates the innate immune function of epithelial cells in an autocrine manner. Nature immunology 391 21993848
2000 Cloning and characterization of IL-17B and IL-17C, two new members of the IL-17 cytokine family. Proceedings of the National Academy of Sciences of the United States of America 276 10639155
2011 IL-17RE is the functional receptor for IL-17C and mediates mucosal immunity to infection with intestinal pathogens. Nature immunology 257 21993849
2013 Keratinocyte overexpression of IL-17C promotes psoriasiform skin inflammation. Journal of immunology (Baltimore, Md. : 1950) 244 23359500
2007 IL-17B and IL-17C are associated with TNF-alpha production and contribute to the exacerbation of inflammatory arthritis. Journal of immunology (Baltimore, Md. : 1950) 164 17982105
2018 Neutralization of IL-17C Reduces Skin Inflammation in Mouse Models of Psoriasis and Atopic Dermatitis. The Journal of investigative dermatology 102 29474945
2017 IL-17C mediates the recruitment of tumor-associated neutrophils and lung tumor growth. Oncogene 102 28346430
2012 Cutting edge: regulation of intestinal inflammation and barrier function by IL-17C. Journal of immunology (Baltimore, Md. : 1950) 82 23024280
2014 Intestinal neuroendocrine cells and goblet cells are mediators of IL-17A-amplified epithelial IL-17C production in human inflammatory bowel disease. Mucosal immunology 74 25492478
2016 MCPIP1/Regnase-1 Restricts IL-17A- and IL-17C-Dependent Skin Inflammation. Journal of immunology (Baltimore, Md. : 1950) 71 27920272
2020 IL-17C/IL-17RE: Emergence of a Unique Axis in TH17 Biology. Frontiers in immunology 70 32174926
2013 The pattern recognition receptor NOD2 mediates Staphylococcus aureus-induced IL-17C expression in keratinocytes. The Journal of investigative dermatology 63 23892590
2018 IL-17C/IL-17 Receptor E Signaling in CD4+ T Cells Promotes TH17 Cell-Driven Glomerular Inflammation. Journal of the American Society of Nephrology : JASN 61 29483158
2014 IL-36γ sustains a proinflammatory self-amplifying loop with IL-17C in anti-TNF-induced psoriasiform skin lesions of patients with Crohn's disease. Inflammatory bowel diseases 59 25299544
2013 IL-17C is a mediator of respiratory epithelial innate immune response. American journal of respiratory cell and molecular biology 58 23221046
2014 Toll-like receptor-mediated airway IL-17C enhances epithelial host defense in an autocrine/paracrine manner. American journal of respiratory cell and molecular biology 56 23944933
2015 IL-17C is required for lethal inflammation during systemic fungal infection. Cellular & molecular immunology 55 26166766
2017 Keratinocytes produce IL-17c to protect peripheral nervous systems during human HSV-2 reactivation. The Journal of experimental medicine 53 28663436
2015 Signaling through IL-17C/IL-17RE is dispensable for immunity to systemic, oral and cutaneous candidiasis. PloS one 47 25849644
2016 Induction of Alternative Proinflammatory Cytokines Accounts for Sustained Psoriasiform Skin Inflammation in IL-17C+IL-6KO Mice. The Journal of investigative dermatology 45 27984037
2020 IL-17C amplifies epithelial inflammation in human psoriasis and atopic eczema. Journal of the European Academy of Dermatology and Venereology : JEADV 42 31793105
2016 IL-17A-mediated expression of epithelial IL-17C promotes inflammation during acute Pseudomonas aeruginosa pneumonia. American journal of physiology. Lung cellular and molecular physiology 36 27694471
2019 IL-17C-mediated innate inflammation decreases the response to PD-1 blockade in a model of Kras-driven lung cancer. Scientific reports 35 31316109
2017 Comparative study of interleukin-17C (IL-17C) and IL-17D in large yellow croaker Larimichthys crocea reveals their similar but differential functional activity. Developmental and comparative immunology 35 28526442
2014 High IL-17E and low IL-17C dermal expression identifies a fibrosis-specific motif common to morphea and systemic sclerosis. PloS one 35 25136988
2018 Rhinovirus and Bacteria Synergistically Induce IL-17C Release from Human Airway Epithelial Cells To Promote Neutrophil Recruitment. Journal of immunology (Baltimore, Md. : 1950) 33 30504421
2020 IL-17C has a pathogenic role in kidney ischemia/reperfusion injury. Kidney international 32 32331702
2020 miR-23a-3p is a Key Regulator of IL-17C-Induced Tumor Angiogenesis in Colorectal Cancer. Cells 32 32492770
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
2017 mRNA cap analogues substituted in the tetraphosphate chain with CX2: identification of O-to-CCl2 as the first bridging modification that confers resistance to decapping without impairing translation. Nucleic acids research 27 28666355
2021 IL-17C in human mucosal immunity: More than just a middle child. Cytokine 26 34293699
2022 Cathelicidin Antimicrobial Peptide LL37 Induces Toll-Like Receptor 8 and Amplifies IL-36γ and IL-17C in Human Keratinocytes. The Journal of investigative dermatology 24 36496195
2018 The roles of IL-17C in T cell-dependent and -independent inflammatory diseases. Scientific reports 24 30356086
2016 IL-17C/IL-17RE Augments T Cell Function in Autoimmune Hepatitis. Journal of immunology (Baltimore, Md. : 1950) 23 27956525
2019 IL-17c is involved in olfactory mucosa responses to Poly(I:C) mimicking virus presence. Brain, behavior, and immunity 21 30776474
2023 IL-17C neutralization protects the kidney against acute injury and chronic injury. EBioMedicine 20 37263138
2019 Toll-like receptor 5-mediated IL-17C expression in intestinal epithelial cells enhances epithelial host defense against F4+ ETEC infection. Veterinary research 20 31221216
2019 Interleukin 17 Receptor E (IL-17RE) and IL-17C Mediate the Recruitment of Neutrophils during Acute Streptococcus pneumoniae Pneumonia. Infection and immunity 17 31481409
2020 Rhinovirus Induces Basolateral Release of IL-17C in Highly Differentiated Airway Epithelial Cells. Frontiers in cellular and infection microbiology 16 32232015
2017 IL-13 regulates IL-17C expression by suppressing NF-κB-mediated transcriptional activation in airway epithelial cells. Biochemical and biophysical research communications 16 29203240
2013 IL-17C expression in nasal epithelial cells of chronic rhinosinusitis with nasal polyposis. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery 15 24013453
2020 IL-17C Protects Nasal Epithelium from Pseudomonas aeruginosa Infection. American journal of respiratory cell and molecular biology 13 31318581
2015 Th17 master transcription factors RORα and RORγ regulate the expression of IL-17C, IL-17D and IL-17F in Cynoglossus semilaevis. Developmental and comparative immunology 13 26547017
2024 IL-17C is a driver of damaging inflammation during Neisseria gonorrhoeae infection of human Fallopian tube. Nature communications 12 38704381
2023 Aldehyde Dehydrogenase 2 Protects the Kidney from Ischemia-Reperfusion Injury by Suppressing the IκBα/NF-κB/IL-17C Pathway. Oxidative medicine and cellular longevity 12 36865346
2013 Primary mucosal melanoma arising from the eustachian tube with CTLA-4, IL-17A, IL-17C, and IL-17E upregulation. Ear, nose, & throat journal 11 23354891
2022 Th17-Derived Cytokines Synergistically Enhance IL-17C Production by the Colonic Epithelium. Journal of immunology (Baltimore, Md. : 1950) 10 36130829
2024 Contribution of IL-17C-mediated macrophage polarization to Type 17 inflammation in neutrophilic asthma. Cell communication and signaling : CCS 9 39568050
2018 IL-17C Mitigates Murine Acute Graft-vs.-Host Disease by Promoting Intestinal Barrier Functions and Treg Differentiation. Frontiers in immunology 9 30534126
2021 Molecular characterization of fish cytokine IL-17C from Amphiprion clarkii and its immunomodulatory effects on the responses to pathogen-associated molecular patterns and bacterial challenges. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 8 34428552
2021 IL-17C and IL-17RE Promote Wound Closure in a Staphylococcus aureus-Based Murine Wound Infection Model. Microorganisms 8 34576717
2023 PepScaf: Harnessing Machine Learning with In Vitro Selection toward De Novo Macrocyclic Peptides against IL-17C/IL-17RE Interaction. Journal of medicinal chemistry 7 37480587
2025 PPARγ accelerates OSCC progression via Th17 polarization and CEBPA/IL-17C signaling. Journal of cancer research and clinical oncology 3 40954243
2023 Nonnegative matrix factorization analysis and multiple machine learning methods identified IL17C and ACOXL as novel diagnostic biomarkers for atherosclerosis. BMC bioinformatics 3 37173646
2025 IL-17C-Mediated Upregulation of SMURF2 Induces Psoriatic Changes in Keratinocytes by Facilitating PPP6C Ubiquitination. Cell biology international 2 40244332
2025 Cyprinid Herpesvirus 2 Infection Activates IL-17C/NF-κB/IFNγ Antiviral Signalling Axis in Caudal Fin Cells of Carassius auratus Gibelio. Journal of fish diseases 1 40637095
2025 IL-17C as a Driver of Inflammation in Psoriasis. Advances in therapy 1 40986185
2021 IL-17 and IL-17C Signaling Protects the Intestinal Epithelium against Diisopropyl Fluorophosphate Exposure in an Acute Model of Gulf War Veterans' Illnesses. Immune network 1 34796039
2020 IL-17C expression and its correlation with pediatric adenoids: a preliminary study. International journal of medical sciences 1 33162788
2026 Synovial macrophage rhoa protects against osteoarthritis by suppressing YAP/IL-17C mediated chondrocyte senescence. Cell biology and toxicology 0 41620554
2025 The protective role of IL-17C in oral squamous cell carcinoma. Translational oncology 0 40974979
2024 [MOR106 alleviates inflammation in mice with atopic dermatitis by blocking the JAK2/STAT3 signaling pathway and inhibiting IL-17C-mediated Tfh cell differentiation]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 38246174

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