GO:0004920 interleukin-10 receptor activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0004920 (interleukin-10 receptor activity) is a molecular function defined as combining with interleukin-10 and transmitting the signal across the membrane to initiate a change in cell activity.
• The receptor is a heterotetramer of two ligand-binding IL10RA (IL-10R1) chains and two signal-transducing IL10RB (IL-10R2) chains.
• IL-10 binding activates JAK1 and TYK2, which phosphorylate STAT3 to drive anti-inflammatory gene expression.
• IL-10 receptor signaling suppresses pro-inflammatory cytokine production and can metabolically reprogram macrophages.
• The receptor is a therapeutic target in cancer, inflammatory disease, and pain, with blockade or agonism being actively explored [2,5,8].
• CRISPR knockout, point-mutation, knock-in, and overexpression models enable causal dissection of IL-10 receptor function [4,6].
Description
Interleukin-10 receptor activity (GO:0004920) is the molecular function by which a cell-surface receptor binds the cytokine interleukin-10 (IL-10) and transmits a signal from one side of the membrane to the other to initiate a change in cell activity. This activity is central to immune regulation because IL-10 is a pleiotropic cytokine with potent anti-inflammatory and immunosuppressive effects. The receptor is a heterotetramer composed of two ligand-binding IL10RA (IL-10R1) subunits and two signal-transducing IL10RB (IL-10R2) subunits. Researchers study GO:0004920 to understand how IL-10 restricts inflammation, how pathogens and tumors exploit this pathway, and how the receptor can be targeted therapeutically [2,5]. The term is also relevant to autophagy, metabolic reprogramming, and neuroimmune pain regulation [3,6,8].
interleukin-10 receptor activity At A Glance
| GO ID | GO:0004920 |
|---|---|
| GO term | interleukin-10 receptor activity |
| Ontology | molecular_function |
| Synonym | IL-10R, IL-10 receptor activity |
| Definition | Combining with interleukin-10 and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity. |
| Major function | Binds IL-10 and initiates intracellular signaling, typically via JAK-STAT3, to suppress inflammation. |
| Receptor composition | Heterotetramer of IL10RA (IL-10R1) and IL10RB (IL-10R2). |
| Primary ligands | Interleukin-10 (IL-10). |
| Key downstream effectors | JAK1, TYK2, STAT3. |
What Is GO:0004920?
In our own words, GO:0004920 describes the function of a receptor that specifically binds interleukin-10 and, upon binding, conveys a signal across the plasma membrane so that the cell changes its behavior. It is a molecular function term, not a process or a component, and it encompasses the ligand-binding and signal-transducing activities of the IL-10 receptor complex.
Why Is interleukin-10 receptor activity Important in Cell Biology?
Interleukin-10 receptor activity is important because it governs a master anti-inflammatory circuit. By binding IL-10 and activating STAT3, the receptor suppresses pro-inflammatory cytokine production and limits tissue damage. This function is exploited by tumors to evade immune attack, making the receptor a target for cancer immunotherapy. It also modulates macrophage metabolism and autophagy, linking cytokine signaling to cellular stress responses [3,6]. Understanding GO:0004920 is therefore essential for immunology, oncology, and inflammatory disease research.
• Controls anti-inflammatory gene programs through STAT3 activation.
• Suppresses pro-inflammatory cytokine production in macrophages and other immune cells.
• Is a checkpoint exploited by colorectal cancer liver metastases to evade immunity.
• Modulates autophagy through ATG16L1-dependent IL10R signaling.
• Regulates meningeal immune-pain circuits and delta opioid receptor expression.
• Provides a structural template for engineering IL-10 variants with decoupled functions.
• Enables discovery of surrogate cytokine agonists for receptor activation.
• Serves as a therapeutic target in inflammatory bowel disease and Crohn disease risk.
• Links cytokine signaling to metabolic reprogramming of macrophages.
• Offers a model system for studying JAK-STAT signal transduction.
What Happens During interleukin-10 receptor activity?
Ligand binding and receptor assembly
In simple terms: IL-10 grabs onto its receptor, pulling the pieces together.
IL-10 binds with high affinity to the IL10RA (IL-10R1) subunit, which then recruits IL10RB (IL-10R2) to form a signaling-competent heterotetramer. This assembly is the first step in transmitting the signal across the membrane.
JAK activation and STAT3 phosphorylation
In simple terms: The receptor wakes up enzymes that pass the message inside.
The assembled receptor brings JAK1 (associated with IL10RA) and TYK2 (associated with IL10RB) into proximity, enabling their activation and phosphorylation of STAT3. Phosphorylated STAT3 dimerizes and translocates to the nucleus to regulate transcription.
Anti-inflammatory gene expression
In simple terms: The signal turns on genes that calm inflammation.
STAT3 drives expression of suppressor of cytokine signaling 3 (SOCS3) and other anti-inflammatory mediators that inhibit pro-inflammatory cytokine production. This transcriptional program is a hallmark of IL-10 receptor activity.
Metabolic reprogramming of macrophages
In simple terms: The receptor changes how immune cells use energy.
IL-10 receptor signaling induces metabolic changes in macrophages, including altered mitochondrial function, that are required for its anti-inflammatory effects. This links GO:0004920 to cellular metabolism.
Autophagy modulation
In simple terms: The receptor can also influence how cells recycle their own parts.
IL10R signaling engages ATG16L1 in a WD40 domain-dependent manner, and this pathway is insensitive to the T300A Crohn disease risk polymorphism. This connects the receptor to autophagy and Crohn disease biology.
Key Genes Involved in GO:0004920 interleukin-10 receptor activity
The following genes and proteins are central to interleukin-10 receptor activity and its downstream effects.
| Gene | Major Role | Research Relevance |
|---|---|---|
| IL10 | Ligand that binds and activates the receptor | Cytokine biology and anti-inflammatory therapy |
| IL10RA | Ligand-binding subunit (IL-10R1) | Receptor assembly and signaling initiation |
| IL10RB | Signal-transducing subunit (IL-10R2) | JAK-TYK2 activation and signal propagation |
| JAK1 | Kinase associated with IL10RA | Phosphorylates STAT3 to drive transcription |
| TYK2 | Kinase associated with IL10RB | Phosphorylates STAT3 to drive transcription |
| STAT3 | Transcription factor downstream of receptor | Mediates anti-inflammatory gene expression |
| SOCS3 | Negative feedback regulator | Limits IL-10 receptor signaling |
| ATG16L1 | Autophagy-related protein | Links IL10R signaling to autophagy and Crohn disease |
| OPRD1 | Delta opioid receptor | Upregulated by meningeal IL-10 to prevent relapsing pain |
| IL10RA variants | Receptor mutations | Altered signaling in inflammatory disease |
| IL10RB variants | Receptor mutations | Altered signaling in inflammatory disease |
| IL10 variants | Ligand mutations | Decoupling pro- and anti-inflammatory functions |
| JAK inhibitors | Pharmacological modulators | Targeting JAK-STAT pathway |
| STAT3 inhibitors | Pharmacological modulators | Targeting downstream transcription |
| SOCS3 mimetics | Potential therapeutics | Modulating feedback inhibition |
| IL-10 agonists | Engineered cytokines | Surrogate agonists for receptor activation |
| IL-10 blockade | Therapeutic strategy | Potentiating antitumor immunity |
How Is interleukin-10 receptor activity Regulated?
Interleukin-10 receptor activity is regulated at multiple levels. SOCS3 provides negative feedback by inhibiting JAK-STAT signaling. The receptor can also be modulated by autophagy-related proteins such as ATG16L1, which influence signaling independently of the T300A Crohn disease risk polymorphism. Additionally, metabolic reprogramming of macrophages downstream of the receptor can feed back on signaling capacity. These layers of regulation ensure that IL-10 responses are context-dependent and self-limiting.
interleukin-10 receptor activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| IL10 | Inflammatory bowel disease | IL10 knockout mouse |
| IL10RA | Early-onset colitis | IL10RA point-mutation knock-in |
| IL10RB | Immune dysregulation | IL10RB knockout cell line |
| ATG16L1 | Crohn disease | ATG16L1 T300A knock-in |
| OPRD1 | Relapsing pain | Meningeal IL-10 overexpression |
Cancer and tumor immune evasion
IL-10 receptor signaling can suppress antitumor immunity, and blockade of IL-10 potentiates antitumor immune function in human colorectal cancer liver metastases. This makes GO:0004920 a target for cancer immunotherapy.
Inflammatory bowel disease and Crohn disease
ATG16L1 WD40 domain-dependent IL10R signaling is insensitive to the T300A Crohn disease risk polymorphism, suggesting that this pathway may be a therapeutic node in Crohn disease. Defects in IL-10 receptor signaling are associated with early-onset inflammatory bowel disease.
Pain and neuroimmune regulation
Upregulation of delta opioid receptor by meningeal interleukin-10 prevents relapsing pain, linking IL-10 receptor activity to pain regulation. This expands the disease relevance of GO:0004920 beyond classical inflammation.
Metabolic and macrophage dysfunction
The anti-inflammatory effect of IL-10 is mediated by metabolic reprogramming of macrophages, and disruption of this process can contribute to inflammatory pathology. Thus, GO:0004920 is relevant to metabolic-inflammatory crosstalk.
From interleukin-10 receptor activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of IL10RA abolish IL-10 signaling? | IL10RA knockout cell line |
| Does a specific point mutation alter JAK-STAT activation? | IL10RA point-mutation knock-in |
| Can a tagged receptor track trafficking? | IL10RA knock-in with fluorescent tag |
| Does overexpression enhance anti-inflammatory effects? | IL10 overexpression vector |
| Can IL-10 variants decouple pro- and anti-inflammatory functions? | Engineered IL-10 knock-in |
| Does IL-10 blockade potentiate antitumor immunity? | Patient-derived tumor explants |
How to Study the interleukin-10 receptor activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Phospho-STAT3 flow cytometry | STAT3 phosphorylation | Receptor activation |
| RNA-seq | Transcriptional changes | Anti-inflammatory gene programs |
| CRISPR knockout screen | Gene essentiality for signaling | Pathway discovery |
| Seahorse assay | Mitochondrial respiration | Metabolic reprogramming |
| Immunoprecipitation | Receptor complex assembly | Protein interactions |
| Western blot | JAK and STAT phosphorylation | Signaling activation |
| ELISA | Cytokine production | Anti-inflammatory effects |
| Autophagy flux assay | ATG16L1-dependent autophagy | Crohn disease modeling |
CRISPR knockout screens
Genome-wide CRISPR knockout screens can identify genes required for IL-10 receptor signaling and downstream anti-inflammatory responses. These screens are useful for discovering modifiers of GO:0004920.
Phospho-STAT3 flow cytometry
Flow cytometry with phospho-STAT3 antibodies measures receptor activity at the single-cell level after IL-10 stimulation. This is a standard readout for GO:0004920.
Transcriptomic profiling
RNA-seq after IL-10 stimulation reveals the gene expression programs driven by receptor activity. This helps define the downstream consequences of GO:0004920.
Metabolic assays
Seahorse and metabolomic assays measure the metabolic reprogramming induced by IL-10 receptor signaling in macrophages. These methods link receptor activity to cellular metabolism.
How CRISPR Can Be Used to Study GO:0004920 interleukin-10 receptor activity
Knockout
CRISPR knockout of IL10RA or IL10RB abolishes IL-10 receptor activity, providing a clean loss-of-function model to study downstream signaling. Knockout of STAT3 similarly blocks the transcriptional response.
Point Mutation
Point mutations in IL10RA or IL10RB can mimic patient variants or disrupt specific signaling motifs, allowing precise structure-function analysis of GO:0004920. For example, mutations that affect JAK binding can uncouple ligand binding from STAT3 activation.
Knock-in
Knock-in of tagged IL10RA or IL10RB enables tracking of receptor localization and trafficking in live cells. Knock-in of disease-associated variants such as ATG16L1 T300A helps model Crohn disease-related signaling.
Overexpression
Overexpression of IL10 or its receptor subunits can amplify signaling and enhance anti-inflammatory effects, useful for gain-of-function studies. Overexpression of engineered IL-10 variants can decouple pro- and anti-inflammatory functions.
How EDITGENE Supports interleukin-10 receptor activity Research
Researchers studying interleukin-10 receptor activity-related genes often need to determine whether a candidate gene is causally involved in signaling, inflammation, or disease. EDITGENE provides CRISPR-based cell models and screening services to enable such causal experiments.
Contact EDITGENE today to design your custom CRISPR model for interleukin-10 receptor activity research.
Frequently Asked Questions About interleukin-10 receptor activity
What is interleukin-10 receptor activity?
It is the molecular function defined by GO:0004920, in which a receptor binds interleukin-10 and transmits a signal across the membrane to change cell activity.
What genes are involved in interleukin-10 receptor activity?
Key genes include IL10, IL10RA, IL10RB, JAK1, TYK2, and STAT3.
What is the GO ID for interleukin-10 receptor activity?
The GO ID is GO:0004920.
How does IL-10 receptor signaling suppress inflammation?
It activates JAK-STAT3 signaling, which drives anti-inflammatory gene expression and metabolic reprogramming of macrophages [1,3].
What diseases are linked to interleukin-10 receptor activity?
It is linked to inflammatory bowel disease, Crohn disease, cancer immune evasion, and relapsing pain [5,6,8].
Can CRISPR be used to study interleukin-10 receptor activity?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are widely used to dissect this pathway [1,4].
What is the structure of the IL-10 receptor?
It is a heterotetramer of two IL10RA and two IL10RB subunits.
How is IL-10 receptor activity regulated?
It is regulated by SOCS3 negative feedback and by autophagy-related proteins such as ATG16L1 [1,6].
What methods measure IL-10 receptor activity?
Phospho-STAT3 flow cytometry, RNA-seq, and metabolic assays are commonly used [1,3].
Why is IL-10 receptor activity important in cancer?
Blockade of IL-10 can potentiate antitumor immune function in colorectal cancer liver metastases.
Conclusion
Interleukin-10 receptor activity (GO:0004920) is a central molecular function in immune regulation, mediating anti-inflammatory signaling through JAK-STAT3 and metabolic reprogramming [1,3]. Its roles in cancer, Crohn disease, and pain make it a high-value target for therapeutic and mechanistic studies [5,6,8]. CRISPR-based models and screening approaches provide powerful tools to dissect this pathway and identify new intervention points.
References
- 1. Moore KW et al.. 2001. Interleukin-10 and the interleukin-10 receptor.. Annu Rev Immunol 19:683-765 PMID: 11244051
- 2. Saxton RA et al.. 2021. Structure-based decoupling of the pro- and anti-inflammatory functions of interleukin-10.. Science 371(6535) PMID: 33737461
- 3. Ip WKE et al.. 2017. Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages.. Science 356(6337):513-519 PMID: 28473584
- 4. Yen M et al.. 2022. Facile discovery of surrogate cytokine agonists.. Cell 185(8):1414-1430.e19 PMID: 35325595
- 5. Sullivan KM et al.. 2023. Blockade of interleukin 10 potentiates antitumour immune function in human colorectal cancer liver metastases.. Gut 72(2):325-337 PMID: 35705369
- 6. 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
- 8. Inyang KE et al.. 2025. Upregulation of delta opioid receptor by meningeal interleukin-10 prevents relapsing pain.. Brain Behav Immun 123:399-410 PMID: 39349285
