GO:0030368 interleukin-17 receptor activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0030368 (interleukin-17 receptor activity) is a molecular function defined as binding any interleukin-17 family cytokine and transmitting the signal across the membrane to initiate a change in cell activity.
• The receptor is a heteromeric complex; IL-17RA is the shared subunit used by several IL-17 cytokines, and IL-17RC is the high-affinity partner for IL-17A and IL-17F.
• Ligand binding activates SEFIR-domain-dependent signaling that converges on NF-kB, MAPK and C/EBP pathways to induce inflammatory and epithelial-remodeling genes.
• IL-17 receptor activity is central to psoriasis, ulcerative colitis, ischaemic stroke and tumor-associated inflammation, making it a validated drug target.
• Autonomous or sustained IL-17 receptor signaling can drive chronic inflammation and disease progression, so receptor activity must be tightly regulated.
• CRISPR knockout, point-mutation, knock-in and overexpression models are the main tools for dissecting IL-17 receptor function in human cells and organoids.
Description
Interleukin-17 receptor activity (GO:0030368) is the molecular function by which a cell-surface receptor binds an interleukin-17 (IL-17) family cytokine and converts that binding event into an intracellular signal. It is annotated as a molecular_function because it describes the biochemical action of the receptor itself, not the downstream cellular response. The receptor is best known as the shared IL-17RA subunit that pairs with IL-17RC to form the functional IL-17A/IL-17F receptor complex. Because IL-17 cytokines are dominant drivers of mucosal and epithelial inflammation, this receptor activity sits at the interface between innate immune sensing and tissue remodeling. Researchers study GO:0030368 to understand how epithelial and stromal cells interpret IL-17 signals during infection, autoimmunity and cancer. In injured epithelium, IL-17 receptor signaling governs hypoxic adaptation and metabolic reprogramming, showing that the receptor is not merely an inflammatory switch but a context-dependent regulator of tissue repair. In chronic disease models, autonomous activation of the IL-17 receptor sustains inflammation and promotes disease progression, which explains why blocking the receptor is therapeutically attractive. This article summarizes the QuickGO definition, the receptor complex composition, the signaling mechanism, the key genes involved, disease links and the CRISPR-based methods used to study interleukin-17 receptor activity. All statements are grounded in the verified literature cited by number.
interleukin-17 receptor activity At A Glance
| GO ID | GO:0030368 |
|---|---|
| GO term | interleukin-17 receptor activity |
| Ontology | molecular_function |
| Synonym | IL-17R; IL-17 receptor activity |
| Definition | Combining with any member of the interleukin-17 family of cytokines and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity. |
| Major function | Cytokine binding and transmembrane signal transduction for IL-17 family ligands |
| Representative receptor subunits | IL-17RA (shared subunit) and IL-17RC (high-affinity partner for IL-17A/IL-17F) |
| Downstream pathways | NF-kB, MAPK and C/EBP-dependent inflammatory gene programs |
| Disease relevance | Psoriasis, ulcerative colitis, ischaemic stroke and inflammation-driven disease progression |
What Is GO:0030368?
In plain terms, interleukin-17 receptor activity is the ability of a cell-surface receptor to grab an IL-17 cytokine on the outside of the cell and pass a signal to the inside. The QuickGO definition states that this activity combines with any member of the interleukin-17 family of cytokines and transmits the signal from one side of the membrane to the other to initiate a change in cell activity. It is a molecular_function term, with synonyms IL-17R and IL-17 receptor activity. The activity is mediated by heteromeric receptor complexes, most commonly IL-17RA paired with IL-17RC, and it initiates intracellular cascades rather than directly catalyzing a chemical reaction.
Why Is interleukin-17 receptor activity Important in Cell Biology?
Interleukin-17 receptor activity is important because it is the first committed step in IL-17 cytokine signaling, and this axis is a validated therapeutic target in autoimmune and inflammatory disease. Blocking the receptor with an anti-IL-17RA antibody produces clinical benefit in palmoplantar pustulosis, confirming that receptor activity is causally linked to human disease. In parallel, experimental models show that IL-17 receptor signaling controls hypoxic adaptation in injured epithelium and can become autonomously activated to sustain chronic inflammation. Understanding GO:0030368 therefore informs drug development, biomarker discovery and mechanistic studies of barrier immunity.
• Defines the receptor-level entry point for all IL-17 family cytokine signals.
• IL-17RA is a shared subunit, so its activity integrates signals from multiple IL-17 cytokines.
• Drives psoriasis-like skin inflammation through the IL-23/IL-17 axis in mouse models.
• Governs hypoxic adaptation and metabolic reprogramming of injured epithelium.
• Autonomous receptor activation sustains inflammation and promotes disease progression.
• Targeting IL-17RA with brodalumab is clinically effective in palmoplantar pustulosis.
• IL-17 receptor signaling contributes to ischaemic stroke pathology.
• Natural compounds such as gingerenone A can attenuate colitis by targeting IL-17RA.
• IL-17 receptor activity links immune sensing to intestinal remodeling circuits.
• Provides a tractable molecular target for CRISPR-based functional genomics.
Molecular Mechanism of interleukin-17 receptor activity
Ligand recognition and receptor complex assembly
In simple terms: The receptor must first catch the IL-17 cytokine and assemble the correct pair of subunits.
Interleukin-17 receptor activity begins when an IL-17 family cytokine binds a heteromeric receptor complex. IL-17RA is the shared subunit used by several IL-17 cytokines, while IL-17RC serves as the high-affinity partner for IL-17A and IL-17F. This combinatorial assembly determines which cytokine signals are received and is the structural basis of the GO:0030368 molecular function.
Transmembrane signal transmission
In simple terms: Once the cytokine is bound, the receptor changes shape and passes the message across the membrane.
Ligand binding induces conformational changes in the receptor ectodomain that are transmitted across the membrane to the cytoplasmic tails. The QuickGO definition captures this step as transmitting the signal from one side of the membrane to the other to initiate a change in cell activity. This transmission depends on the SEFIR domain, a conserved cytoplasmic module that nucleates downstream signaling complexes.
Activation of NF-kB, MAPK and C/EBP programs
In simple terms: The receptor switches on transcription factors that turn inflammatory genes on.
Downstream of the receptor, signaling converges on NF-kB, MAPK and C/EBP transcription factors, which induce inflammatory cytokines, chemokines and antimicrobial peptides. In injured epithelium, this program is coupled to hypoxic adaptation, showing that the receptor output is tailored to the tissue context. Autonomous activation of this pathway can sustain inflammation and promote disease progression.
Feedback and context-dependent regulation
In simple terms: The cell can dial the receptor signal up or down depending on the situation.
IL-17 receptor activity is not a simple on/off switch; it is modulated by receptor abundance, ligand availability and intracellular feedback. Sustained or autonomous activation has been observed in disease settings, where it perpetuates inflammation. In the intestine, IL-17 receptor signaling participates in tuft cell-ILC2 circuits that drive remodeling, illustrating how the same activity can support homeostasis or pathology depending on context.
Key Genes Involved in GO:0030368 interleukin-17 receptor activity
The following genes encode the receptor subunits, ligands and core signaling components that define interleukin-17 receptor activity and its downstream effects.
| Gene | Major Role | Research Relevance |
|---|---|---|
| IL17RA | Shared receptor subunit for multiple IL-17 cytokines | Central to GO:0030368; target of brodalumab and gingerenone A |
| IL17RC | High-affinity partner for IL-17A and IL-17F | Determines ligand specificity of the receptor complex |
| IL17A | Cytokine ligand that activates the receptor | Prototypical IL-17 family ligand in inflammation |
| IL17F | Cytokine ligand that activates the receptor | Shares IL-17RA/IL-17RC complex with IL-17A |
| IL17B | IL-17 family cytokine | Contributes to the ligand repertoire of GO:0030368 |
| IL17C | IL-17 family cytokine | Epithelial cytokine that signals through IL-17 receptor complexes |
| IL17D | IL-17 family cytokine | Less-characterized ligand of the IL-17 family |
| IL17E | IL-17 family cytokine (IL-25) | Signals through IL-17RA/IL-17RB in type 2 immunity |
| IL23A | Cytokine subunit upstream of IL-17 production | Drives IL-23/IL-17 axis in psoriasis models |
| IL12B | Cytokine subunit upstream of IL-17 production | Part of IL-23 complex that sustains IL-17 signaling |
| NFKB1 | Transcription factor downstream of receptor | Mediates inflammatory gene induction |
| MAPK1 | Kinase downstream of receptor | Transmits MAPK signals from IL-17 receptor |
| MAPK14 | Stress-activated kinase downstream of receptor | Contributes to IL-17-induced inflammatory output |
| CEBPB | Transcription factor downstream of receptor | Cooperates with NF-kB at IL-17 target genes |
| ACT1 | Adaptor protein that binds the SEFIR domain | Nucleates downstream signaling complexes |
| TRAF6 | E3 ligase in IL-17 receptor signaling | Links receptor activation to NF-kB |
| HIF1A | Hypoxia-inducible factor downstream of IL-17 | Mediates hypoxic adaptation of injured epithelium |
How Is interleukin-17 receptor activity Regulated?
Interleukin-17 receptor activity is regulated at multiple levels. Receptor abundance and heterodimer composition control which cytokines can be sensed, with IL-17RA serving as the shared subunit and IL-17RC providing high-affinity binding for IL-17A and IL-17F. Intracellular feedback through the SEFIR domain and its adaptor complexes shapes the strength and duration of signaling, and autonomous activation of this pathway can sustain inflammation and promote disease progression. In injured epithelium, the receptor output is coupled to hypoxic adaptation, indicating that metabolic and oxygen-sensing pathways modulate the response. In the intestine, IL-17 receptor signaling is embedded in tuft cell-ILC2 circuits that drive remodeling, showing that tissue context is a key regulator of the activity.
interleukin-17 receptor activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| IL17RA | Psoriasis and palmoplantar pustulosis | Keratinocyte knockout and anti-IL-17RA antibody treatment |
| IL17RA | Ulcerative colitis and barrier dysfunction | Intestinal epithelial knockout with gingerenone A treatment |
| IL17A | Ischaemic stroke neuroinflammation | Middle cerebral artery occlusion in IL-17A knockout mice |
| IL17RA | Autonomous inflammation and disease progression | Knock-in of constitutively active receptor in immune cells |
| IL17E | Intestinal remodeling and type 2 immunity | Tuft cell-ILC2 circuit perturbation in organoids |
Psoriasis and IL-23/IL-17 axis inflammation
Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis, directly implicating interleukin-17 receptor activity in disease pathogenesis. The clinical success of brodalumab, an anti-IL-17RA monoclonal antibody, in palmoplantar pustulosis confirms that blocking this receptor activity produces therapeutic benefit in humans. These findings establish GO:0030368 as a validated target in IL-17-driven skin disease.
Ulcerative colitis and intestinal barrier function
Gingerenone A attenuates ulcerative colitis by targeting IL-17RA to inhibit inflammation and restore intestinal barrier function, showing that receptor activity can be modulated pharmacologically in colitis. IL-17 receptor signaling also participates in tuft cell-ILC2 circuits that drive small intestinal remodeling, linking the receptor to epithelial renewal and barrier maintenance. Together these studies position GO:0030368 as a key node in intestinal inflammation and repair.
Ischaemic stroke and neuroinflammation
Interleukin-17 and its receptor activity contribute to ischaemic stroke pathology, where IL-17 signaling amplifies neuroinflammation and tissue injury. Because the receptor is the entry point for IL-17 signals, targeting GO:0030368 is a plausible strategy to limit post-stroke inflammatory damage.
Chronic inflammation and disease progression
Autonomous activation of interleukin-17 receptor signaling sustains inflammation and promotes disease progression, indicating that dysregulated receptor activity can become self-perpetuating. In injured epithelium, IL-17 governs hypoxic adaptation, further linking receptor activity to tissue remodeling under stress. These observations highlight the need for precise regulation of GO:0030368 in chronic disease settings.
From interleukin-17 receptor activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of IL-17RA abolish IL-17-induced inflammatory gene expression? | IL17RA knockout cell line or organoid |
| Which residues in the SEFIR domain are required for signal transmission? | Point-mutation knock-in of SEFIR-domain variants |
| Can a tagged receptor track endogenous IL-17RA trafficking? | Knock-in of an epitope-tagged IL17RA allele |
| Does overexpression of IL-17RC sensitize cells to IL-17A? | IL17RC overexpression cell model |
| Which genes mediate hypoxic adaptation downstream of the receptor? | IL17RA knockout followed by RNA-seq under hypoxia |
| Can autonomous receptor activation drive chronic inflammation? | Knock-in of constitutively active receptor in mouse models |
How to Study the interleukin-17 receptor activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Global transcriptional changes | Identify IL-17 receptor-dependent gene programs |
| CRISPR knockout library screening | Gene requirement for receptor signaling | Discover novel regulators of GO:0030368 |
| Co-immunoprecipitation | Protein-protein interactions in receptor complex | Map SEFIR-domain adaptor assembly |
| Phospho-protein assays | Activation of MAPK and NF-kB pathways | Quantify receptor signal strength |
| Immunofluorescence imaging | Subcellular localization of receptor subunits | Track IL-17RA trafficking in epithelial cells |
| Organoid culture | Epithelial barrier and remodeling responses | Model intestinal IL-17 receptor function |
| Mouse disease models | In vivo contribution of receptor activity | Test psoriasis, colitis and stroke phenotypes |
| Flow cytometry | Immune cell activation and cytokine production | Measure downstream inflammatory output |
Transcriptomic profiling of receptor-dependent programs
RNA-seq of cells or organoids with and without IL-17 receptor activation reveals the gene programs controlled by GO:0030368. This approach has been used to show that IL-17 governs hypoxic adaptation of injured epithelium, identifying downstream metabolic and stress-response genes. Comparing IL17RA knockout and wild-type cells under IL-17 stimulation isolates receptor-specific transcriptional output.
CRISPR functional genomics and library screening
Pooled CRISPR knockout libraries can systematically test which genes are required for IL-17 receptor signaling. This is particularly useful for identifying novel regulators of the pathway and for validating candidate targets in inflammatory disease models. Library screening also helps distinguish receptor-proximal components from downstream effectors.
Protein interaction and signaling assays
Co-immunoprecipitation, proximity labeling and phospho-protein assays map the receptor complex and its downstream signaling. These methods have been used to define the SEFIR-domain-dependent assembly of adaptor complexes that transmit IL-17 receptor signals. They are essential for confirming that a candidate gene product physically participates in GO:0030368.
In vivo disease models and imaging
Mouse models of psoriasis, colitis and stroke allow researchers to test how receptor activity contributes to disease. Imiquimod-induced psoriasis-like skin inflammation is a standard model for the IL-23/IL-17 axis, while middle cerebral artery occlusion models ischaemic stroke. Imaging of tagged receptors and reporter mice can localize receptor activity in tissues.
How CRISPR Can Be Used to Study GO:0030368 interleukin-17 receptor activity
Knockout
CRISPR knockout of IL17RA or IL17RC abolishes interleukin-17 receptor activity and provides a clean loss-of-function background for testing downstream phenotypes. Knockout epithelial cells and organoids have been used to show that IL-17 receptor signaling is required for hypoxic adaptation and inflammatory gene induction. Knockout models are also the starting point for rescue experiments with wild-type or mutant receptor alleles.
Point Mutation
Point mutations in the SEFIR domain or ligand-binding interface can dissect which residues are required for signal transmission versus ligand binding. Such knock-in models are valuable for separating receptor-proximal signaling events from downstream amplification. Point-mutation approaches also help validate drug-binding sites on IL-17RA.
Knock-in
Knock-in of epitope-tagged or fluorescently tagged IL17RA allows endogenous receptor tracking without overexpression artifacts. Tagged knock-in lines can be used for imaging, co-immunoprecipitation and proximity labeling to define the receptor interactome. Knock-in of disease-associated or constitutively active variants can model autonomous receptor activation.
Overexpression
Overexpression of IL17RA or IL17RC can sensitize cells to IL-17 cytokines and amplify receptor-dependent transcriptional programs. This approach is useful for testing whether a candidate gene is sufficient to enhance GO:0030368 signaling. Overexpression models also support high-throughput screens for receptor modulators.
How EDITGENE Supports interleukin-17 receptor activity Research
Researchers studying interleukin-17 receptor activity-related genes often need to determine whether a candidate gene is causally involved in receptor signaling, inflammatory gene induction or disease progression. EDITGENE provides the CRISPR cell models and screening services needed to move from correlation to causation in this pathway.
Contact EDITGENE today to design your custom CRISPR model for interleukin-17 receptor activity research.
Frequently Asked Questions About interleukin-17 receptor activity
What is interleukin-17 receptor activity?
It is the molecular function defined by GO:0030368, in which a cell-surface receptor binds an IL-17 family cytokine and transmits the signal across the membrane to initiate a change in cell activity.
What genes are involved in interleukin-17 receptor activity?
Key genes include IL17RA, IL17RC, IL17A, IL17F and downstream effectors such as NFKB1, MAPK1 and CEBPB.
Which receptor subunits form the IL-17 receptor complex?
IL-17RA is the shared subunit and IL-17RC is the high-affinity partner for IL-17A and IL-17F.
What diseases are linked to interleukin-17 receptor activity?
Psoriasis, palmoplantar pustulosis, ulcerative colitis, ischaemic stroke and chronic inflammation-driven disease progression.
How is interleukin-17 receptor activity regulated?
It is regulated by receptor abundance, heterodimer composition, SEFIR-domain adaptor complexes and tissue context such as hypoxia and intestinal remodeling circuits.
What drugs target interleukin-17 receptor activity?
Brodalumab is an anti-IL-17RA monoclonal antibody that blocks receptor activity and is effective in palmoplantar pustulosis.
How do researchers study GO:0030368?
Common methods include RNA-seq, CRISPR knockout screening, co-immunoprecipitation, phospho-protein assays, organoid culture and mouse disease models.
Can CRISPR knockout abolish IL-17 receptor signaling?
Yes, knockout of IL17RA or IL17RC removes receptor activity and provides a loss-of-function background for rescue and mechanistic experiments.
What is the role of IL-17 receptor activity in the intestine?
It contributes to intestinal inflammation and barrier function, and participates in tuft cell-ILC2 circuits that drive small intestinal remodeling.
Why is interleukin-17 receptor activity a drug target?
Because it is the first committed step in IL-17 signaling and blocking it produces clinical benefit in inflammatory disease.
Conclusion
Interleukin-17 receptor activity (GO:0030368) is the molecular function that allows cells to sense IL-17 family cytokines and convert that signal into inflammatory and tissue-remodeling programs. The receptor complex, centered on IL-17RA and IL-17RC, activates NF-kB, MAPK and C/EBP pathways and is causally linked to psoriasis, colitis, ischaemic stroke and chronic disease progression. Because the pathway is both mechanistically tractable and clinically validated, it is an excellent subject for CRISPR-based functional studies. Knockout, point-mutation, knock-in and overexpression models, combined with RNA-seq and library screening, can define which genes are required for receptor activity and which are sufficient to drive disease.
References
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- 2. Luo Q et al.. 2023. An autonomous activation of interleukin-17 receptor signaling sustains inflammation and promotes disease progression.. Immunity 56(9):2006-2020.e6 PMID: 37473759
- 3. van der Fits L et al.. 2009. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis.. J Immunol 182(9):5836-45 PMID: 19380832
- 4. Fossiez F et al.. 1998. Interleukin-17.. Int Rev Immunol 16(5-6):541-51 PMID: 9646176
- 5. Liang J et al.. 2024. Gingerenone A Attenuates Ulcerative Colitis via Targeting IL-17RA to Inhibit Inflammation and Restore Intestinal Barrier Function.. Adv Sci (Weinh) 11(28):e2400206 PMID: 38639442
- 6. Zhang Q et al.. 2021. Interleukin-17 and ischaemic stroke.. Immunology 162(2):179-193 PMID: 32935861
- 7. Okubo Y et al.. 2024. Efficacy and Safety of Brodalumab, an Anti-interleukin-17 Receptor A Monoclonal Antibody, for Palmoplantar Pustulosis: 16-Week Results of a Randomized Clinical Trial.. Am J Clin Dermatol 25(5):837-847 PMID: 38954226
- 8. Schneider C et al.. 2018. A Metabolite-Triggered Tuft Cell-ILC2 Circuit Drives Small Intestinal Remodeling.. Cell 174(2):271-284.e14 PMID: 29887373
