GO:1905571 interleukin-10 receptor complex: Components, Assembly and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1905571 describes the interleukin-10 receptor complex, a cell-surface protein assembly that binds IL-10 and consists of at least a dimeric IL-10 ligand, an alpha chain (IL10RA) and a beta chain (IL10RB), with optional kinase subunits.
• The alpha chain IL10RA binds IL-10 with high affinity, while IL10RB is a shared receptor chain also used by other interleukin receptors.
• Cryo-EM and structure-based studies have revealed how IL-10 engages its receptor and provided a blueprint for engineering IL-10 variants with decoupled pro- and anti-inflammatory activities.
• The IL-10 receptor complex is a central node in immune regulation, and its blockade can potentiate antitumour immunity in human colorectal cancer liver metastases.
• Surrogate cytokine agonists and cytokine adaptors can redirect signalling through the IL-10 receptor complex, illustrating its tractability as a therapeutic target.
• CRISPR-based knockout, knock-in, point-mutation and overexpression models are essential for dissecting the causal roles of IL10RA, IL10RB and downstream signalling components in health and disease.
Description
The interleukin-10 receptor complex (GO:1905571) is a cell-surface protein assembly that binds the cytokine interleukin-10 (IL-10) and initiates intracellular signalling. According to the QuickGO definition, this complex consists of, at a minimum, a dimeric interleukin, an alpha chain and a beta chain, as well as optional additional kinase subunits; the alpha chain binds IL-10 with high affinity and subsequently binds the common beta receptor chain that forms part of multiple interleukin receptors. The complex is therefore a key entry point for IL-10-mediated immune regulation and a focal point for structural and functional studies of cytokine receptor assembly. Researchers study GO:1905571 because it sits at the interface of anti-inflammatory and pro-inflammatory signalling, and because its components are shared with other cytokine receptor systems. Structural work has shown that IL-10 engages its receptor in a defined geometry, and that this geometry can be engineered to decouple the pro- and anti-inflammatory functions of IL-10. In parallel, functional studies in human colorectal cancer liver metastases have demonstrated that blockade of interleukin 10 potentiates antitumour immune function, highlighting the therapeutic relevance of this receptor complex. The complex is also a model system for understanding how cytokine receptors achieve specificity and how surrogate agonists or adaptors can rewire signalling from the cell surface. Because IL10RB is a shared chain, the interleukin-10 receptor complex intersects with broader cytokine networks, making it important for immunology, oncology and infectious disease research.
interleukin-10 receptor complex At A Glance
| GO ID | GO:1905571 |
|---|---|
| GO term | interleukin-10 receptor complex |
| Ontology | cellular_component |
| Synonym | IL-10 receptor complex; IL-10-receptor complex; IL10 receptor complex; interleukin-10-receptor complex |
| Major function | Binds interleukin-10 and initiates receptor-mediated signalling through an alpha chain and a shared beta chain |
| Alpha chain | IL10RA binds IL-10 with high affinity and subsequently binds the common beta receptor chain |
| Beta chain | IL10RB is a shared chain that forms part of multiple interleukin receptors |
| Optional subunits | Additional kinase subunits may be present in the complex |
| Structural basis | Cryo-EM structures of the IL-10 receptor complex provide a blueprint for ligand engineering |
What Is GO:1905571?
In our own words, GO:1905571 (interleukin-10 receptor complex) is a protein complex that binds interleukin-10 and is composed of at least a dimeric interleukin ligand, an alpha chain and a beta chain, with optional additional kinase subunits. The alpha chain binds IL-10 with high affinity and then associates with the common beta receptor chain that is shared by multiple interleukin receptors.
Why Is interleukin-10 receptor complex Important in Cell Biology?
The interleukin-10 receptor complex is important because it is the primary gateway for IL-10 signalling, a pathway that controls immune tolerance, inflammation and antitumour immunity. Structural and functional studies have shown that the complex can be engineered or blocked to shift immune responses, making it a high-value target for immunotherapy and for understanding cytokine receptor assembly.
• It is the receptor complex that binds IL-10, a central anti-inflammatory cytokine.
• Its alpha chain IL10RA binds IL-10 with high affinity and determines ligand specificity.
• Its beta chain IL10RB is shared with other interleukin receptors, linking IL-10 to broader cytokine networks.
• Blockade of interleukin 10 potentiates antitumour immune function in human colorectal cancer liver metastases.
• Structure-based decoupling of IL-10 functions enables separation of pro- and anti-inflammatory activities.
• Surrogate cytokine agonists can activate the IL-10 receptor complex and related receptors.
• Cytokine adaptors can redirect immune signalling through receptor complexes such as this one.
• Inflammatory and anti-inflammatory cytokines, including IL-10, bidirectionally modulate amygdala circuits regulating anxiety.
• Rewiring STAT signalling from the cell surface with Trikine immunotherapeutics targets receptor complexes like the IL-10 receptor complex.
• The complex is relevant to infectious disease studies, including Mycobacterium avium subsp. paratuberculosis infection of mammary epithelial cells.
Structure and Composition of interleukin-10 receptor complex
Ligand binding by the alpha chain
In simple terms: The alpha chain grabs IL-10 first and holds it tightly.
The interleukin-10 receptor complex is defined by the high-affinity binding of IL-10 to the alpha chain, IL10RA. This initial interaction is a prerequisite for assembly of the complete signalling complex and determines the specificity of the receptor for IL-10 over other cytokines.
Recruitment of the shared beta chain
In simple terms: After grabbing IL-10, the alpha chain calls in a shared partner chain.
Following ligand binding, the alpha chain binds the common beta receptor chain, IL10RB, which forms part of multiple interleukin receptors. This shared usage means that the interleukin-10 receptor complex is integrated into a wider cytokine receptor network.
Dimeric interleukin ligand
In simple terms: IL-10 itself is a two-part molecule that bridges receptor chains.
The QuickGO definition specifies that the complex consists of, at a minimum, a dimeric interleukin, an alpha chain and a beta chain. The dimeric nature of IL-10 is central to how it engages and orientates the receptor chains for signalling.
Optional kinase subunits
In simple terms: Additional kinase proteins can join the complex to pass the signal inside the cell.
The definition notes that optional additional kinase subunits may be present in the complex. These kinase subunits are important for propagating the signal from the cell surface to intracellular pathways, and their inclusion reflects the dynamic composition of the receptor complex.
Structural blueprint from cryo-EM
In simple terms: High-resolution imaging shows exactly how the parts fit together.
Cryo-EM structure of the IL-10 receptor complex provides a blueprint for ligand engineering, revealing the architecture of the ligand-receptor assembly. This structural information has been used to design IL-10 variants with decoupled pro- and anti-inflammatory functions.
Key Genes Involved in GO:1905571 interleukin-10 receptor complex
The following genes and proteins are central to the interleukin-10 receptor complex and its signalling context.
| Gene | Major Role | Research Relevance |
|---|---|---|
| IL10 | Encodes the interleukin-10 cytokine ligand that binds the receptor complex | Ligand engineering and decoupling of pro- and anti-inflammatory functions |
| IL10RA | Encodes the alpha chain that binds IL-10 with high affinity | Determines ligand specificity and high-affinity binding |
| IL10RB | Encodes the shared beta chain used by multiple interleukin receptors | Links IL-10 signalling to broader cytokine networks |
| JAK1 | Kinase subunit that can associate with the receptor complex | Optional kinase subunit in the complex definition |
| TYK2 | Kinase subunit that can associate with the receptor complex | Optional kinase subunit in the complex definition |
| STAT3 | Transcription factor activated downstream of IL-10 receptor signalling | Mediates transcriptional responses to IL-10 |
| STAT1 | Transcription factor activated downstream of cytokine receptor signalling | Contributes to IL-10 receptor signalling outputs |
| SOCS3 | Negative regulator of cytokine signalling | Feedback regulation of IL-10 receptor signalling |
| IL10RA variants | Altered alpha chain function | Structure-based decoupling of IL-10 functions |
| IL10RB variants | Altered shared beta chain function | Surrogate cytokine agonist discovery |
| IL6ST | Shared signalling chain in related cytokine receptors | Context for shared receptor chain biology |
| IFNAR1 | Interferon receptor chain | Comparative cytokine receptor biology |
| IL2RB | Interleukin-2 receptor beta chain | Comparative shared chain biology |
| IL2RG | Common gamma chain shared by multiple interleukin receptors | Comparative shared chain biology |
| IL10Rα | Protein product of IL10RA studied in infection models | Mycobacterium avium subsp. paratuberculosis infection of mammary epithelial cells |
| Trikine receptors | Engineered receptor constructs that rewire STAT signalling | Trikine immunotherapeutics targeting receptor complexes |
| Cytokine adaptors | Engineered molecules that redirect immune signalling | Redirecting immune signalling through receptor complexes |
How Is interleukin-10 receptor complex Regulated?
The interleukin-10 receptor complex is regulated at multiple levels, including ligand availability, receptor chain expression and downstream feedback. Structure-based studies have shown that the geometry of IL-10 engagement with its receptor can be engineered to decouple pro- and anti-inflammatory functions, indicating that receptor assembly and ligand-receptor contacts are key regulatory nodes. Blockade of interleukin 10 can potentiate antitumour immune function, demonstrating that the pathway is dynamically regulated in the tumour microenvironment. In addition, cytokine adaptors and surrogate agonists can redirect signalling through the complex, showing that its output can be rewired from the cell surface. Inflammatory and anti-inflammatory cytokines, including IL-10, bidirectionally modulate amygdala circuits regulating anxiety, indicating that receptor complex activity is integrated into broader physiological regulation.
interleukin-10 receptor complex and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| IL10 | Cancer and antitumour immunity | Knockout or overexpression in colorectal cancer liver metastasis models |
| IL10RA | Infectious disease and host-pathogen interaction | Knockout in mammary epithelial cell lines infected with Mycobacterium avium subsp. paratuberculosis |
| IL10RB | Cytokine receptor signalling and immunotherapy | Knock-in of engineered variants for surrogate agonist studies |
| STAT3 | Immunotherapy and STAT signalling rewiring | Point mutation or knockout in Trikine immunotherapeutic models |
| Cytokine adaptors | Immune signalling redirection | Overexpression of adaptor constructs in immune cells |
Cancer and antitumour immunity
Blockade of interleukin 10 potentiates antitumour immune function in human colorectal cancer liver metastases, highlighting the interleukin-10 receptor complex as a target for cancer immunotherapy. Structure-based decoupling of the pro- and anti-inflammatory functions of interleukin-10 provides a rationale for engineering IL-10 variants that retain antitumour activity while reducing unwanted inflammatory effects.
Infectious disease
The role of interleukin-10 receptor alpha (IL10Rα) has been studied in Mycobacterium avium subsp. paratuberculosis infection of a mammary epithelial cell line, linking the receptor complex to host-pathogen interactions. This work illustrates how the interleukin-10 receptor complex can influence epithelial responses during infection.
Neuropsychiatric and anxiety-related circuits
Inflammatory and anti-inflammatory cytokines bidirectionally modulate amygdala circuits regulating anxiety, indicating that IL-10 and its receptor complex can influence neural circuit activity. This connects the interleukin-10 receptor complex to neuroimmune regulation of behaviour.
Immunotherapy engineering
Rewiring STAT signaling from the cell surface with Trikine immunotherapeutics and redirecting immune signaling with cytokine adaptors demonstrate that the interleukin-10 receptor complex can be targeted by engineered molecules to achieve desired immune outcomes. Surrogate cytokine agonists can also activate the complex, expanding the therapeutic toolkit.
From interleukin-10 receptor complex-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of IL10RA abolish IL-10 receptor complex signalling? | IL10RA knockout cell line |
| Does a specific point mutation in IL10RB alter shared chain function? | IL10RB point-mutation knock-in |
| Can an engineered IL-10 variant decouple pro- and anti-inflammatory functions? | IL10 knock-in or overexpression of engineered ligand |
| Does blockade of IL-10 potentiate antitumour immunity? | IL10 knockout or antibody blockade in colorectal cancer liver metastasis models |
| Can cytokine adaptors redirect signalling through the complex? | Overexpression of cytokine adaptors in immune cells |
| Can Trikine immunotherapeutics rewire STAT signalling from the cell surface? | Knock-in of Trikine receptor constructs |
How to Study the interleukin-10 receptor complex Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Cryo-EM | Three-dimensional structure of the receptor complex | Blueprint for ligand engineering |
| Functional immune assays | Immune cell activation and tumour cell killing | Testing IL-10 blockade in colorectal cancer liver metastases |
| Surrogate cytokine agonist discovery | Activation of cytokine receptors | Identifying agonists for the IL-10 receptor complex |
| Cytokine adaptor engineering | Redirection of immune signalling | Redirecting signalling through receptor complexes |
| Trikine immunotherapeutics | STAT signalling rewiring from the cell surface | Engineering receptor complex outputs |
| Knockout models | Loss-of-function effects on receptor complex signalling | Dissecting IL10RA and IL10RB function |
| Knock-in models | Effects of specific mutations or engineered variants | Testing point mutations and engineered ligands |
| Overexpression models | Gain-of-function effects on receptor complex activity | Studying cytokine adaptors and ligands |
Structural biology (cryo-EM)
Cryo-EM structure of the IL-10 receptor complex provides a blueprint for ligand engineering, revealing the architecture of the ligand-receptor assembly. This method is used to determine how IL-10 engages IL10RA and IL10RB and to guide the design of engineered variants.
Functional immune assays
Blockade of interleukin 10 potentiates antitumour immune function in human colorectal cancer liver metastases, demonstrating the use of functional immune assays to test the consequences of targeting the receptor complex. These assays measure immune cell activation and tumour cell killing.
Surrogate cytokine agonist discovery
Facile discovery of surrogate cytokine agonists enables the identification of molecules that activate the interleukin-10 receptor complex and related receptors. This approach is used to probe receptor activation and to develop therapeutic candidates.
Cytokine adaptor and Trikine engineering
Redirecting immune signaling with cytokine adaptors and rewiring STAT signaling from the cell surface with Trikine immunotherapeutics are methods for engineering the signalling output of receptor complexes such as the interleukin-10 receptor complex. These techniques measure changes in STAT activation and downstream immune responses.
How CRISPR Can Be Used to Study GO:1905571 interleukin-10 receptor complex
Knockout
CRISPR knockout of IL10RA or IL10RB can abolish interleukin-10 receptor complex signalling, enabling researchers to test the causal role of the complex in immune regulation and disease. Knockout of IL10 itself can be used to remove ligand availability and to study the consequences of pathway loss.
Point Mutation
CRISPR point mutation can be used to introduce specific amino acid changes in IL10RA, IL10RB or downstream signalling components, allowing structure-function studies of the interleukin-10 receptor complex. Such models are valuable for testing hypotheses derived from cryo-EM structures and for engineering receptor variants with altered signalling properties.
Knock-in
CRISPR knock-in can be used to insert engineered IL-10 variants, tagged receptor chains or Trikine receptor constructs into cells, enabling precise control over interleukin-10 receptor complex composition and signalling. Knock-in models are particularly useful for studying ligand-receptor geometry and for developing therapeutic candidates.
Overexpression
CRISPR overexpression or stable overexpression of IL10, IL10RA, IL10RB, cytokine adaptors or engineered ligands can be used to amplify interleukin-10 receptor complex signalling and to study gain-of-function phenotypes. Overexpression models are also used to test whether a candidate molecule can redirect immune signalling through the complex.
How EDITGENE Supports interleukin-10 receptor complex Research
Researchers studying interleukin-10 receptor complex-related genes often need to determine whether a candidate gene is causally involved in receptor assembly, signalling or disease. EDITGENE provides CRISPR-based knockout, point-mutation, knock-in and overexpression cell models, as well as CRISPR library screening and bioinformatics services, to support such studies.
Contact EDITGENE today to design your custom CRISPR model for interleukin-10 receptor complex research.
Frequently Asked Questions About interleukin-10 receptor complex
What is the interleukin-10 receptor complex?
The interleukin-10 receptor complex (GO:1905571) is a cell-surface protein complex that binds interleukin-10 and consists of at least a dimeric interleukin, an alpha chain and a beta chain, with optional additional kinase subunits.
What genes are involved in the interleukin-10 receptor complex?
The core genes are IL10, which encodes the ligand, IL10RA, which encodes the high-affinity alpha chain, and IL10RB, which encodes the shared beta chain.
What is the function of IL10RA in the interleukin-10 receptor complex?
IL10RA binds IL-10 with high affinity and subsequently binds the common beta receptor chain that forms part of multiple interleukin receptors.
What is the function of IL10RB in the interleukin-10 receptor complex?
IL10RB is the shared beta chain that forms part of multiple interleukin receptors and is recruited after IL-10 binds the alpha chain.
How is the interleukin-10 receptor complex structured?
Cryo-EM structure of the IL-10 receptor complex provides a blueprint for ligand engineering, revealing the architecture of the ligand-receptor assembly.
Can the interleukin-10 receptor complex be targeted for cancer therapy?
Blockade of interleukin 10 potentiates antitumour immune function in human colorectal cancer liver metastases, indicating that targeting this pathway is a promising cancer immunotherapy strategy.
What diseases are associated with the interleukin-10 receptor complex?
The complex has been linked to cancer, infectious disease and neuropsychiatric circuits, including antitumour immunity in colorectal cancer liver metastases and Mycobacterium avium subsp. paratuberculosis infection.
How can CRISPR be used to study the interleukin-10 receptor complex?
CRISPR knockout, point mutation, knock-in and overexpression models can be used to dissect the roles of IL10, IL10RA, IL10RB and downstream signalling components in receptor complex function.
What are surrogate cytokine agonists for the interleukin-10 receptor complex?
Surrogate cytokine agonists are engineered molecules that can activate the interleukin-10 receptor complex and related receptors, enabling facile discovery of receptor activators.
How do cytokine adaptors and Trikine immunotherapeutics target the interleukin-10 receptor complex?
Cytokine adaptors and Trikine immunotherapeutics can redirect immune signalling and rewire STAT signalling from the cell surface, targeting receptor complexes such as the interleukin-10 receptor complex.
Conclusion
The interleukin-10 receptor complex (GO:1905571) is a defined cell-surface assembly that binds IL-10 through a high-affinity alpha chain and a shared beta chain, with optional kinase subunits. Its structural and functional characterization has provided a blueprint for ligand engineering and has highlighted its potential as a therapeutic target in cancer, infectious disease and neuroimmune regulation. CRISPR-based knockout, point-mutation, knock-in and overexpression models, together with structural and functional assays, are essential for dissecting the causal roles of IL10, IL10RA, IL10RB and downstream signalling components. EDITGENE provides these models and services to accelerate research on the interleukin-10 receptor complex.
References
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- 4. Lee B et al.. 2025. Inflammatory and anti-inflammatory cytokines bidirectionally modulate amygdala circuits regulating anxiety.. Cell 188(8):2190-2202.e15 PMID: 40199321
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- 7. Fong A et al.. 2024. The role of interleukin-10 receptor alpha (IL10Rα) in Mycobacterium avium subsp. paratuberculosis infection of a mammary epithelial cell line.. BMC Genom Data 25(1):58 PMID: 38867147
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