GO:0045513 interleukin-27 binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0045513 (interleukin-27 binding) is a molecular function defined as binding to interleukin-27, the heterodimeric cytokine composed of IL-27p28 and EBI3 subunits.
• IL-27 binding initiates signaling through the receptor complex IL-27Rα (WSX-1) and gp130, activating JAK/STAT and other pathways.
• IL-27 binding has context-dependent roles in infectious disease, autoimmunity, and cancer, with both pro-inflammatory and anti-inflammatory effects.
• Key genes involved in IL-27 binding and signaling include IL27, EBI3, IL27RA, IL6ST, JAK1, JAK2, STAT1, and STAT3.
• IL-27 binding is implicated in neonatal sepsis, tuberculosis, HIV resistance, pulmonary fibrosis, and central nervous system diseases.
• CRISPR-based models (knockout, knock-in, overexpression) enable causal dissection of IL-27 binding and its downstream effects.
Description
Interleukin-27 (IL-27) is a heterodimeric cytokine belonging to the IL-12 family, composed of the p28 subunit (IL-27p28, encoded by IL27) and the Epstein-Barr virus-induced gene 3 (EBI3) subunit. The molecular function GO:0045513, interleukin-27 binding, describes the selective interaction of a protein or receptor with IL-27. This binding event is the first step in IL-27-mediated signaling and is critical for immune regulation. Researchers study IL-27 binding to understand how this cytokine modulates host defense, inflammation, and tissue homeostasis. The IL-27 receptor complex, composed of IL-27Rα (WSX-1) and gp130, binds IL-27 with high affinity, triggering intracellular signaling cascades. Dysregulated IL-27 binding has been associated with a range of pathological conditions, including neonatal sepsis, tuberculosis, HIV infection, pulmonary fibrosis, and neurological disorders. Thus, GO:0045513 represents a focal point for investigating cytokine-receptor interactions and their therapeutic potential.
interleukin-27 binding At A Glance
| GO ID | GO:0045513 |
|---|---|
| GO term | interleukin-27 binding |
| Ontology | molecular_function |
| Synonym | IL-27 binding |
| Definition | Binding to interleukin-27. |
| Major function | Mediates the interaction of IL-27 with its receptor complex, initiating signaling. |
| Related cytokine | Interleukin-27 (IL-27), a heterodimer of p28 and EBI3. |
| Receptor components | IL-27Rα (WSX-1) and gp130. |
| Downstream pathways | JAK/STAT, MAPK, and others. |
What Is GO:0045513?
According to the Gene Ontology, GO:0045513 (interleukin-27 binding) is defined as the molecular function of binding to interleukin-27. In other words, it is the ability of a protein or molecular complex to physically interact with IL-27, a heterodimeric cytokine. This binding event is typically mediated by specific receptor subunits such as IL-27Rα and gp130, and it initiates downstream signaling.
Why Is interleukin-27 binding Important in Cell Biology?
Interleukin-27 binding is a critical molecular event that governs the pleiotropic functions of IL-27 in immunity and disease. Because IL-27 can exert both pro-inflammatory and anti-inflammatory effects depending on context, understanding its binding to receptors is essential for deciphering its role in infections, autoimmunity, and cancer. Moreover, IL-27 binding is being explored as a target for therapeutic intervention in conditions such as tuberculosis, sepsis, and fibrosis.
• IL-27 binding initiates signaling that shapes T cell differentiation and immune responses.
• It is involved in host defense against bacterial infections, including tuberculosis.
• IL-27 binding contributes to neonatal sepsis transcriptome signatures.
• It plays a role in HIV resistance mechanisms in dendritic cells.
• IL-27 binding is implicated in pulmonary fibrosis via platelet-macrophage circuits.
• It modulates neuronal survival in central nervous system diseases.
• Dysregulated IL-27 binding is associated with autoimmune and inflammatory disorders.
• IL-27 binding can influence tumor immunity and cancer progression.
• It is a target for vaccine and immunotherapeutic development.
• Studying IL-27 binding aids in understanding cytokine-receptor specificity and signaling.
Molecular Mechanism of interleukin-27 binding
Ligand recognition and receptor assembly
In simple terms: IL-27 binds to its receptor like a key in a lock, bringing two receptor parts together.
Interleukin-27 binding is mediated by the high-affinity receptor complex composed of IL-27Rα (WSX-1) and gp130. The p28 subunit of IL-27 primarily engages IL-27Rα, while EBI3 interacts with gp130, leading to receptor heterodimerization. This assembly is essential for signal transduction.
Activation of JAK/STAT signaling
In simple terms: Once IL-27 is bound, it switches on signaling proteins inside the cell.
Upon IL-27 binding, receptor-associated Janus kinases (JAK1, JAK2, TYK2) are activated and phosphorylate STAT1 and STAT3, which then translocate to the nucleus to regulate gene expression. This pathway is central to IL-27's biological effects.
Modulation of immune cell function
In simple terms: IL-27 binding tells immune cells what to do, like fight infections or calm inflammation.
IL-27 binding influences T helper cell differentiation, promotes IL-10 production, and regulates B cell functions, including regulatory B cell activity. These effects are context-dependent and contribute to immune homeostasis.
Context-dependent outcomes in disease
In simple terms: The same IL-27 binding can be helpful or harmful depending on the disease.
In tuberculosis, IL-27 binding can suppress protective immunity, while in sepsis it may exacerbate inflammation. In pulmonary fibrosis, IL-27 binding is part of a platelet-macrophage circuit that fuels fibrosis. Thus, the consequences of IL-27 binding are highly context-specific.
Key Genes Involved in GO:0045513 interleukin-27 binding
The following genes encode proteins that directly bind IL-27 or mediate its downstream signaling, and are commonly studied in the context of GO:0045513.
| Gene | Major Role | Research Relevance |
|---|---|---|
| IL27 | Encodes IL-27p28 subunit | Ligand for IL-27 binding; knockout models study loss of signaling |
| EBI3 | Encodes EBI3 subunit of IL-27 | Required for IL-27 heterodimer formation and binding |
| IL27RA | Encodes IL-27Rα (WSX-1) receptor subunit | Primary binding partner for IL-27; knockout abolishes signaling |
| IL6ST | Encodes gp130 receptor subunit | Shared receptor subunit; mediates IL-27 binding and signaling |
| JAK1 | Janus kinase 1 | Phosphorylates STATs upon IL-27 binding |
| JAK2 | Janus kinase 2 | Participates in IL-27-induced signaling |
| TYK2 | Tyrosine kinase 2 | Contributes to IL-27 receptor signaling |
| STAT1 | Signal transducer and activator of transcription 1 | Key transcription factor activated by IL-27 binding |
| STAT3 | Signal transducer and activator of transcription 3 | Mediates IL-27-induced gene expression |
| BATF3 | Transcription factor | Regulates regulatory B cell functions downstream of IL-27 binding |
| SPTBN1 | Spectrin beta, non-erythrocytic 1 | Implicated in IL-27-induced HIV resistance in dendritic cells |
| YB-1 | Y-box binding protein 1 | May modulate IL-27 responses |
| TGFB1 | Transforming growth factor beta 1 | Cooperates with IL-27 in pulmonary fibrosis |
| IL10 | Interleukin-10 | Induced by IL-27 binding; anti-inflammatory cytokine |
| IFNG | Interferon gamma | Regulated by IL-27 binding in T cells |
| GZMB | Granzyme B | Effector molecule influenced by IL-27 signaling |
| PRF1 | Perforin 1 | Cytotoxic effector modulated by IL-27 |
| FOXP3 | Forkhead box P3 | Regulatory T cell marker; IL-27 binding can influence Tregs |
How Is interleukin-27 binding Regulated?
IL-27 binding and signaling are regulated at multiple levels. Expression of the IL-27 subunits (IL27 and EBI3) is induced by Toll-like receptor agonists and inflammatory cytokines. The receptor components IL27RA and IL6ST are also dynamically regulated. Negative feedback mechanisms include SOCS proteins and phosphatases that dampen JAK/STAT signaling. Additionally, IL-27 binding can be modulated by soluble receptors or binding proteins, though these are less characterized.
interleukin-27 binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| IL27 | Tuberculosis, sepsis | Il27 knockout mouse; macrophage infection models |
| IL27RA | Autoimmunity, infection | Il27ra knockout mouse; T cell differentiation assays |
| EBI3 | Inflammatory diseases | Ebi3 knockout mouse; cytokine production assays |
| SPTBN1 | HIV resistance | SPTBN1 knockdown dendritic cells; HIV infection assays |
| TGFB1 | Pulmonary fibrosis | Tgfb1 knockout mouse; bleomycin-induced fibrosis model |
Interleukin-27 binding in infectious diseases
IL-27 binding plays diverse roles in bacterial infections. In tuberculosis, IL-27 binding can suppress protective Th1 responses, potentially exacerbating disease. In neonatal sepsis, IL-27-dependent transcriptome signatures have been identified, suggesting a role in sepsis pathogenesis. Conversely, IL-27 binding may enhance HIV resistance in dendritic cells through mechanisms involving SPTBN1, autophagy, and YB-1.
Interleukin-27 binding in fibrosis
Externalized histones fuel pulmonary fibrosis via a platelet-macrophage circuit involving TGFβ1 and IL-27. IL-27 binding in this context promotes fibrotic responses, highlighting its potential as a therapeutic target.
Interleukin-27 binding in neurological disorders
IL-27 binding has been implicated in the regulation of neuronal survival in central nervous system diseases. Depending on the context, IL-27 can be neuroprotective or neurotoxic, influencing outcomes in neuroinflammation and neurodegeneration.
Interleukin-27 binding in cancer and immune regulation
IL-27 binding affects tumor immunity and immune cell functions. It can promote anti-tumor responses or, conversely, support immune evasion, depending on the tumor microenvironment. Regulatory B cells with BATF3-dependent functions are influenced by IL-27 binding, linking it to immune tolerance.
From interleukin-27 binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of IL-27 binding affect T cell differentiation? | IL27ra knockout mouse or CRISPR KO in primary T cells |
| What is the role of IL-27 binding in sepsis? | IL27 knockout mouse; neonatal sepsis models |
| How does IL-27 binding influence HIV resistance? | SPTBN1 knockout dendritic cells; HIV infection assays |
| Does IL-27 binding promote fibrosis? | Il27ra knockout mouse; bleomycin-induced pulmonary fibrosis |
| What are the downstream targets of IL-27 binding? | STAT1/STAT3 knockout cells; RNA-seq after IL-27 stimulation |
| Can IL-27 binding be modulated therapeutically? | Knock-in mice expressing mutant IL-27; overexpression models |
How to Study the interleukin-27 binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Global gene expression changes | Identify IL-27-induced transcriptome |
| Co-IP/MS | Protein-protein interactions | Discover novel IL-27 binding partners |
| Flow cytometry | Cell surface binding and signaling | Measure IL-27 binding to receptor |
| Western blot | STAT phosphorylation | Assess JAK/STAT activation |
| ELISA | Cytokine production | Quantify IL-10, IFN-γ after IL-27 stimulation |
| CRISPR knockout | Gene function | Dissect role of IL27RA, STAT1 in IL-27 binding |
| Proximity ligation assay | In situ protein interactions | Visualize IL-27-receptor binding |
| Luciferase reporter | Transcriptional activity | Measure STAT-mediated transcription |
Transcriptomic profiling
RNA-seq and microarray analyses are used to identify gene expression changes induced by IL-27 binding. For example, IL-27-dependent transcriptome signatures have been characterized in neonatal sepsis.
Proteomic and interactomic approaches
Co-immunoprecipitation, mass spectrometry, and proximity labeling can identify proteins that bind IL-27 or its receptor complex, providing insights into the molecular function GO:0045513.
Flow cytometry and imaging
Flow cytometry and immunofluorescence are used to detect IL-27 binding to cell surfaces and to monitor downstream signaling events such as STAT phosphorylation.
Functional assays
Proliferation, cytokine production, and cytotoxicity assays assess the functional consequences of IL-27 binding in immune cells. These are often combined with CRISPR knockout of IL27RA or IL6ST.
How CRISPR Can Be Used to Study GO:0045513 interleukin-27 binding
Knockout
CRISPR knockout of IL27RA, IL6ST, or STAT1 can abolish IL-27 binding and downstream signaling, enabling causal studies of GO:0045513 in immune cells.
Point Mutation
Point mutations in the IL-27 binding interface of IL27RA or IL6ST can be introduced to dissect specific residues required for ligand interaction, providing mechanistic insights.
Knock-in
Knock-in of tagged IL27RA or IL6ST allows for affinity purification and imaging of the IL-27 receptor complex in live cells, facilitating studies of binding dynamics.
Overexpression
Overexpression of IL27, EBI3, or IL27RA can enhance IL-27 binding and signaling, useful for gain-of-function experiments and therapeutic screening.
How EDITGENE Supports interleukin-27 binding Research
Researchers studying interleukin-27 binding-related genes often need to determine whether a candidate gene is causally involved in IL-27 signaling or is merely a bystander. EDITGENE provides a comprehensive suite of CRISPR-based services to enable such causal investigations with high precision and reproducibility.
Contact EDITGENE today to design your custom CRISPR model for interleukin-27 binding research.
Frequently Asked Questions About interleukin-27 binding
What is interleukin-27 binding?
Interleukin-27 binding (GO:0045513) is the molecular function of physically interacting with the cytokine IL-27, typically by its receptor complex.
What genes are involved in interleukin-27 binding?
Key genes include IL27, EBI3, IL27RA, IL6ST, JAK1, JAK2, STAT1, and STAT3.
What is the GO ID for interleukin-27 binding?
The Gene Ontology ID for interleukin-27 binding is GO:0045513.
How does interleukin-27 binding affect immune cells?
It activates JAK/STAT signaling, influencing T cell differentiation, B cell function, and cytokine production.
Is interleukin-27 binding pro-inflammatory or anti-inflammatory?
It can be both, depending on the context and cell type.
What diseases are associated with interleukin-27 binding?
Tuberculosis, neonatal sepsis, HIV infection, pulmonary fibrosis, and neurological disorders.
How can I study interleukin-27 binding in the lab?
Use CRISPR knockout of receptor genes, RNA-seq, flow cytometry, and functional assays.
What are the receptor components for interleukin-27 binding?
IL-27Rα (WSX-1) and gp130 form the receptor complex.
Can interleukin-27 binding be targeted therapeutically?
Yes, it is being explored as a target in infections, autoimmunity, and fibrosis.
What CRISPR models are available for interleukin-27 binding research?
Knockout, point mutation, knock-in, and overexpression models can be custom-generated.
Conclusion
Interleukin-27 binding (GO:0045513) is a fundamental molecular function that initiates the diverse biological effects of IL-27. Its context-dependent roles in infection, autoimmunity, fibrosis, and neurological disease make it a compelling target for basic and translational research. Leveraging CRISPR-based models and advanced bioinformatics, researchers can dissect the precise mechanisms and therapeutic potential of IL-27 binding.
References
- 2. Povroznik JM et al.. 2023. Interleukin-27-dependent transcriptome signatures during neonatal sepsis.. Front Immunol 14:1124140 PMID: 36891292
- 3. Ritter K et al.. 2021. Interleukin-27 in Tuberculosis: A Sheep in Wolf's Clothing?. Front Immunol 12:810602 PMID: 35116036
- 4. Morita Y et al.. 2021. Interleukin-27 and Its Diverse Effects on Bacterial Infections.. Front Immunol 12:678515 PMID: 34079555
- 5. Yan H et al.. 2025. Ligand-receptor interactions induce and mediate regulatory functions of BATF3(+) B cells.. Sci Adv 11(41):eadx9917 PMID: 41061049
- 6. Nortey AN et al.. 2022. Exploring the role of interleukin-27 as a regulator of neuronal survival in central nervous system diseases.. Neural Regen Res 17(10):2149-2152 PMID: 35259821
- 7. Imamichi T et al.. 2023. Interleukin-27-induced HIV-resistant dendritic cells suppress reveres transcription following virus entry in an SPTBN1, autophagy, and YB-1 independent manner.. PLoS One 18(11):e0287829 PMID: 37910521
- 8. Riehl DR et al.. 2023. Externalized histones fuel pulmonary fibrosis via a platelet-macrophage circuit of TGFβ1 and IL-27.. Proc Natl Acad Sci U S A 120(40):e2215421120 PMID: 37756334
