GO:0005141 interleukin-10 receptor binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0005141 (interleukin-10 receptor binding) is a molecular function defined as binding to an interleukin-10 receptor [QuickGO].
• The principal ligand is the cytokine IL-10, which engages the heterodimeric receptor IL10RA/IL10RB to initiate anti-inflammatory signaling.
• Structural studies show that IL-10 uses distinct receptor-binding interfaces to decouple its anti-inflammatory and pro-inflammatory activities.
• IL10R signaling is modulated by autophagy-related proteins such as ATG16L1, linking this function to Crohn disease risk.
• IL-10 receptor binding also occurs in non-immune cells, including somatosensory neurons, where it controls CCL2 release and inflammatory responses.
• Viral and cellular proteins such as Ebi3 and TIGIT can interfere with or modulate IL-10 receptor binding and downstream function [4,5].
Description
Interleukin-10 receptor binding (GO:0005141) is a molecular function that describes the binding of a ligand to an interleukin-10 receptor. The best-characterized ligand for this function is the cytokine interleukin-10 (IL-10), which binds to the heterodimeric receptor complex composed of IL10RA (IL-10R1) and IL10RB (IL-10R2). This interaction is the first step in a signaling cascade that typically suppresses inflammatory responses, making it a central node in immune regulation. Researchers study this function to understand how anti-inflammatory signals are initiated, how they are subverted in disease, and how they can be targeted therapeutically [1,2]. Beyond classical immune cells, IL-10 receptor binding has been observed in other cell types, such as somatosensory neurons, where it modulates neuroimmune crosstalk. The function is also relevant to cancer biology, as IL-10 receptor expression has been characterized on B-cell chronic lymphocytic leukemia cells. Structural and biochemical analyses have revealed that IL-10 can be engineered to separate its anti-inflammatory and pro-inflammatory properties, highlighting the therapeutic potential of targeting this binding event. Additionally, accessory proteins like Ebi3 can bind to IL-10 and limit its function, providing another layer of regulation. Understanding GO:0005141 therefore encompasses not only the canonical IL-10–IL10R interaction but also the broader network of molecules that modulate it.
interleukin-10 receptor binding At A Glance
| GO ID | GO:0005141 |
|---|---|
| GO term | interleukin-10 receptor binding |
| Ontology | molecular_function |
| Synonym | IL-10, interleukin-10 receptor ligand |
| Major function | Binding to an interleukin-10 receptor, initiating downstream signaling |
| Primary ligand | Interleukin-10 (IL-10) |
| Receptor complex | Heterodimer of IL10RA and IL10RB |
| Related disease | Crohn disease, B-cell chronic lymphocytic leukemia [2,6] |
| Modulatory proteins | ATG16L1, Ebi3, TIGIT [2,4,5] |
What Is GO:0005141?
According to the Gene Ontology, GO:0005141 (interleukin-10 receptor binding) is defined as the binding to an interleukin-10 receptor. This molecular function is carried out by ligands such as the cytokine IL-10, which specifically recognizes and binds to the extracellular domains of the IL-10 receptor complex. The term encompasses any interaction where a molecule directly binds to an interleukin-10 receptor, including binding by IL-10 itself, engineered variants, or other proteins that associate with the receptor [1,5].
Why Is interleukin-10 receptor binding Important in Cell Biology?
Interleukin-10 receptor binding is a critical molecular event that governs the initiation of anti-inflammatory signaling, which is essential for maintaining immune homeostasis and preventing excessive tissue damage. Dysregulation of this binding event is implicated in autoimmune and inflammatory diseases, including Crohn disease, where genetic variants in ATG16L1 affect IL10R signaling. The function also plays a role in neuroimmune interactions, as IL-10 signaling in somatosensory neurons controls chemokine release and inflammatory responses. Furthermore, IL-10 receptor binding is relevant to cancer, as receptor expression is detectable on malignant B cells in chronic lymphocytic leukemia. Understanding the structural basis of this binding has enabled the design of IL-10 variants with decoupled pro- and anti-inflammatory activities, offering new therapeutic avenues. The interaction is also targeted by immunoregulatory proteins such as TIGIT, which promotes the generation of immunoregulatory dendritic cells. Thus, GO:0005141 is a focal point for research in immunology, oncology, and neuroscience.
• Initiates anti-inflammatory signaling through the IL10RA/IL10RB receptor complex.
• Structural insights allow decoupling of pro- and anti-inflammatory functions of IL-10.
• Genetic variants in ATG16L1 affect IL10R signaling and are linked to Crohn disease.
• IL-10 receptor binding in somatosensory neurons modulates CCL2 release and inflammation.
• TIGIT promotes immunoregulatory dendritic cells via IL-10-related mechanisms.
• Ebi3 binding to IL-10 limits its function, providing a regulatory checkpoint.
• IL-10 receptor expression on B-cell chronic lymphocytic leukemia cells is a disease marker.
• PD-L1 has been identified as a fungal-binding receptor, highlighting broader ligand-receptor interactions.
• Comparison of IL-22 and IL-10 soluble receptor complexes reveals shared and distinct binding features.
Molecular Mechanism of interleukin-10 receptor binding
Ligand Recognition and Binding Interface
In simple terms: IL-10 grabs onto its receptor using specific contact points.
IL-10 binds to the extracellular domain of IL10RA with high affinity, forming the primary ligand-receptor interface. Structural studies have identified the specific residues on IL-10 that mediate this interaction, and engineering these interfaces can selectively abolish either anti-inflammatory or pro-inflammatory signaling. The binding is characterized by a large buried surface area and involves both hydrophobic and electrostatic interactions.
Receptor Heterodimerization and Signaling Initiation
In simple terms: After IL-10 binds, the two receptor chains come together to start a signal.
IL-10 first binds to IL10RA, which then recruits IL10RB to form a signaling-competent heterodimer. This assembly triggers phosphorylation of JAK kinases associated with the receptor intracellular domains, leading to STAT3 activation and downstream anti-inflammatory gene expression. The binding event is therefore the trigger for the entire signaling cascade.
Modulation by Accessory Proteins
In simple terms: Other proteins can interfere with or tweak IL-10 binding to its receptor.
Ebi3, a subunit of IL-27 and IL-35, can bind to IL-10 and limit its function, acting as a decoy or modulator of IL-10 receptor binding. Similarly, TIGIT expressed on T cells promotes the generation of mature immunoregulatory dendritic cells, which may involve IL-10-related pathways. These accessory proteins add layers of regulation to the core binding event.
Autophagy-Related Regulation of IL10R Signaling
In simple terms: Proteins involved in cellular cleanup can affect how IL-10 receptor signals.
ATG16L1, a key autophagy protein, is required for optimal IL10R signaling. The WD40 domain of ATG16L1 mediates this effect, and the T300A Crohn disease risk polymorphism does not impair this specific function, suggesting that IL10R signaling is insensitive to this variant. This links autophagy machinery to the regulation of interleukin-10 receptor binding and downstream responses.
Tissue-Specific Binding and Function
In simple terms: IL-10 can bind to receptors on cells outside the immune system, like neurons.
In somatosensory neurons, IL-10 receptor binding controls the release of CCL2, a chemokine that recruits inflammatory cells. This indicates that GO:0005141 is not restricted to immune cells but also operates in the nervous system to modulate inflammation. Such tissue-specific contexts expand the biological significance of this molecular function.
Key Genes Involved in GO:0005141 interleukin-10 receptor binding
The following genes and proteins are directly involved in or modulate interleukin-10 receptor binding and its downstream effects.
| Gene | Major Role | Research Relevance |
|---|---|---|
| IL10 | Primary ligand that binds to IL-10 receptor | Central to anti-inflammatory signaling; engineered variants decouple functions |
| IL10RA | Ligand-binding subunit of the IL-10 receptor | Mediates high-affinity binding of IL-10 |
| IL10RB | Signaling subunit of the IL-10 receptor | Recruited after IL-10 binding to initiate signaling |
| ATG16L1 | Autophagy protein that supports IL10R signaling | Crohn disease risk gene; WD40 domain required for IL10R function |
| TIGIT | Immunoregulatory receptor on T cells | Promotes immunoregulatory dendritic cells via IL-10-related pathways |
| EBI3 | IL-27/IL-35 subunit that binds IL-10 | Limits IL-10 function by sequestering it |
| JAK1 | Kinase associated with IL10RA | Phosphorylates STAT3 downstream of receptor binding |
| STAT3 | Transcription factor activated by IL-10 signaling | Mediates anti-inflammatory gene expression |
| CCL2 | Chemokine regulated by IL-10 in neurons | Links IL-10 receptor binding to neuroinflammation |
| PD-L1 | Immune checkpoint protein with fungal-binding ability | Broader context of ligand-receptor interactions |
| IL22 | Cytokine related to IL-10 | Comparison of soluble receptor complexes reveals shared features |
| IL22RA1 | Receptor for IL-22 | Structural comparison with IL-10 receptor complexes |
| IL20RB | Shared receptor subunit for IL-20 family cytokines | Involved in IL-22 and IL-10 receptor complex comparisons |
| SOCS3 | Negative regulator of cytokine signaling | Feedback inhibition of IL-10 signaling |
| PIAS3 | Modulator of STAT3 activity | Regulates IL-10-induced transcription |
How Is interleukin-10 receptor binding Regulated?
Interleukin-10 receptor binding and its downstream signaling are tightly regulated at multiple levels. The binding event itself can be modulated by accessory proteins such as Ebi3, which binds to IL-10 and limits its function. Autophagy-related proteins like ATG16L1 are required for optimal IL10R signaling, and the Crohn disease risk variant T300A does not impair this specific pathway. Negative feedback loops involving SOCS3 and PIAS3 attenuate STAT3 activation following receptor engagement. Additionally, TIGIT-mediated pathways can influence the generation of immunoregulatory dendritic cells, indirectly affecting IL-10 receptor binding contexts. Tissue-specific regulation is evident in somatosensory neurons, where IL-10 receptor binding controls CCL2 release.
interleukin-10 receptor binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ATG16L1 | Crohn disease | Knock-in of T300A variant in intestinal epithelial cells |
| IL10RA | Inflammatory bowel disease | Knockout in primary human macrophages |
| IL10 | Autoimmunity and inflammation | Overexpression of engineered IL-10 variants in mice |
| TIGIT | Cancer immunotherapy | Knockout in T cells followed by dendritic cell co-culture |
| EBI3 | Immune regulation | Knockout in dendritic cells to assess IL-10 sequestration |
Crohn Disease and Inflammatory Bowel Disease
Genetic variants in ATG16L1, a key autophagy gene, are associated with Crohn disease. ATG16L1 is required for optimal IL10R signaling, and the WD40 domain mediates this function. Notably, the T300A risk polymorphism does not affect IL10R signaling, suggesting that the disease association may involve other ATG16L1 functions. This highlights the complexity of IL-10 receptor binding in inflammatory bowel disease pathogenesis.
B-cell Chronic Lymphocytic Leukemia
IL-10 receptor expression has been characterized on B-cell chronic lymphocytic leukemia (B-CLL) cells. The presence of these receptors suggests that IL-10 receptor binding may influence the survival or proliferation of malignant B cells, making it a potential therapeutic target or biomarker in B-CLL.
Neuroinflammation and Pain
In somatosensory neurons, IL-10 receptor binding controls the release of CCL2, a chemokine that promotes inflammatory responses. This indicates that IL-10 signaling in the nervous system can modulate neuroinflammation and potentially pain, expanding the disease relevance of GO:0005141 beyond classical immune disorders.
Cancer Immunotherapy and Checkpoint Regulation
TIGIT, an immune checkpoint receptor, suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells, a process that may involve IL-10-related pathways. Additionally, PD-L1 has been identified as a fungal-binding receptor, illustrating the broader context of ligand-receptor interactions in immune regulation. These findings link interleukin-10 receptor binding to cancer immunotherapy and host-pathogen interactions.
From interleukin-10 receptor binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does a candidate gene regulate IL-10 receptor binding? | Knockout cell line (e.g., IL10RA KO) followed by binding assays |
| Does a point mutation affect IL-10 binding affinity? | Point-mutation knock-in of IL10 or IL10RA variants |
| Can a tagged IL-10 receptor be used for imaging? | Knock-in of fluorescent or epitope tag at IL10RA locus |
| Does overexpression of Ebi3 limit IL-10 function? | Overexpression of EBI3 in dendritic cells |
| Is ATG16L1 required for IL10R signaling? | Knockout of ATG16L1 in intestinal epithelial cells |
| Does IL-10 receptor binding in neurons control CCL2? | Conditional knockout of IL10RA in somatosensory neurons |
How to Study the interleukin-10 receptor binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Surface Plasmon Resonance | Binding affinity and kinetics | Characterizing IL-10 variants |
| Flow Cytometry | Cell surface receptor binding | Quantifying IL-10 receptor on B-CLL cells |
| Co-immunoprecipitation | Protein-protein interaction | Detecting IL-10/IL10RA complexes |
| CRISPR Knockout Screening | Gene requirement for binding/signaling | Identifying modulators like ATG16L1 |
| ELISA | Cytokine levels | Measuring IL-10 in supernatants |
| Immunofluorescence | Subcellular localization | Visualizing receptor internalization |
| RNA-seq | Transcriptional changes | Assessing downstream STAT3 targets |
| Proteomics | Protein interaction networks | Mapping IL-10 receptor complex components |
Surface Plasmon Resonance (SPR) and Biolayer Interferometry (BLI)
These biophysical methods measure real-time binding kinetics between IL-10 and its receptor. They are used to determine affinity constants (KD) and to assess the impact of mutations on binding.
Flow Cytometry and Ligand Binding Assays
Flow cytometry with fluorescently labeled IL-10 can quantify receptor binding on the surface of live cells, including immune cells and cancer cell lines.
Immunoprecipitation and Western Blotting
Co-immunoprecipitation of IL-10 with IL10RA/IL10RB followed by western blotting confirms physical interaction and receptor heterodimerization.
CRISPR Screening and Functional Genomics
Genome-wide CRISPR knockout screens can identify genes that modulate IL-10 receptor binding or downstream signaling, such as ATG16L1.
How CRISPR Can Be Used to Study GO:0005141 interleukin-10 receptor binding
Knockout
CRISPR knockout of IL10RA, IL10RB, or IL10 in cell lines abolishes interleukin-10 receptor binding and downstream signaling, providing a clean background to study the function of this molecular event. Knockout of ATG16L1 can reveal its role in supporting IL10R signaling.
Point Mutation
Introducing point mutations into IL10 or its receptor can dissect the binding interface. For example, mutations that disrupt specific contacts can decouple anti-inflammatory and pro-inflammatory functions, as shown by structure-based engineering. The T300A variant in ATG16L1 can be introduced to test its effect on IL10R signaling.
Knock-in
Knock-in of epitope tags or fluorescent proteins at the endogenous IL10RA locus allows real-time tracking of receptor expression and binding in live cells. This approach is useful for imaging and biochemical studies.
Overexpression
Overexpression of IL-10 or its receptor subunits can amplify binding signals for biochemical assays. Overexpression of Ebi3 can be used to study its inhibitory effect on IL-10 function. Similarly, overexpression of TIGIT in T cells can modulate immunoregulatory dendritic cell generation.
How EDITGENE Supports interleukin-10 receptor binding Research
Researchers studying interleukin-10 receptor binding-related genes often need to determine whether a candidate gene is causally involved in the binding event or its downstream signaling. EDITGENE provides a comprehensive suite of CRISPR-based services to enable such functional studies, from generating knockout cell lines to engineering precise point mutations and knock-ins.
Contact EDITGENE today to design your custom CRISPR model for interleukin-10 receptor binding research.
Frequently Asked Questions About interleukin-10 receptor binding
What is GO:0005141?
GO:0005141 is the Gene Ontology molecular function term for interleukin-10 receptor binding, defined as binding to an interleukin-10 receptor [QuickGO].
What genes are involved in interleukin-10 receptor binding?
Key genes include IL10 (the ligand), IL10RA and IL10RB (receptor subunits), and modulators such as ATG16L1, EBI3, and TIGIT [1,2,4,5].
What is the function of interleukin-10 receptor binding?
It initiates anti-inflammatory signaling by bringing together IL10RA and IL10RB, leading to STAT3 activation and suppression of inflammatory responses.
Which diseases are associated with interleukin-10 receptor binding?
Crohn disease, B-cell chronic lymphocytic leukemia, and neuroinflammatory conditions have been linked to this function [2,3,6].
How can I study interleukin-10 receptor binding in the lab?
Common methods include surface plasmon resonance, flow cytometry, co-immunoprecipitation, and CRISPR knockout screens [1,2,6].
What is the role of ATG16L1 in IL-10 receptor binding?
ATG16L1 supports IL10R signaling through its WD40 domain, and the T300A Crohn disease variant does not impair this specific function.
Can IL-10 receptor binding be targeted therapeutically?
Yes, engineered IL-10 variants that decouple pro- and anti-inflammatory functions are being explored for therapy.
What is the difference between IL-10 and IL-22 receptor binding?
Both cytokines share structural similarities, but their soluble receptor complexes differ in composition and binding specificity.
Does IL-10 receptor binding occur in neurons?
Yes, IL-10 receptor binding in somatosensory neurons controls CCL2 release and modulates inflammatory responses.
How does Ebi3 affect IL-10 receptor binding?
Ebi3 binds to IL-10 and limits its function, acting as a negative regulator of IL-10 receptor binding.
Conclusion
Interleukin-10 receptor binding (GO:0005141) is a fundamental molecular function that initiates anti-inflammatory signaling through the IL10RA/IL10RB receptor complex. Its importance spans immune homeostasis, inflammatory diseases, cancer, and neurobiology, with structural insights enabling engineered variants for therapy. Understanding the regulatory layers, including ATG16L1, Ebi3, and TIGIT, provides a rich area for future research. EDITGENE offers comprehensive CRISPR services to facilitate functional studies of this critical binding event.
References
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- 2. Serramito-Gómez I et al.. 2022. ATG16L1 WD40 domain-dependent IL10R (interleukin 10 receptor) signaling is insensitive to the T300A Crohn disease risk polymorphism.. Autophagy 18(12):3023-3030 PMID: 35311452
- 3. de Souza S et al.. 2024. Interleukin-10 signaling in somatosensory neurons controls CCL2 release and inflammatory response.. Brain Behav Immun 116:193-202 PMID: 38081433
- 4. Yu X et al.. 2009. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells.. Nat Immunol 10(1):48-57 PMID: 19011627
- 5. Scott EN et al.. 2024. Ebi3 Binding to IFN-γ and IL-10 Limits Their Function.. J Immunol 213(8):1115-1124 PMID: 39240167
- 6. Jurlander J et al.. 1997. Characterization of interleukin-10 receptor expression on B-cell chronic lymphocytic leukemia cells.. Blood 89(11):4146-52 PMID: 9166857
- 7. Li K et al.. 2024. Profiling phagosome proteins identifies PD-L1 as a fungal-binding receptor.. Nature 630(8017):736-743 PMID: 38839956
- 8. Logsdon NJ et al.. 2002. Comparison of interleukin-22 and interleukin-10 soluble receptor complexes.. J Interferon Cytokine Res 22(11):1099-112 PMID: 12513909
