GO:0016515 interleukin-13 receptor activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0016515 (interleukin-13 receptor activity) is a molecular function defined as combining with interleukin-13 and transmitting the signal across the membrane to initiate a change in cell activity.
• IL-13 signals through two principal receptor complexes: the type I receptor (IL-4Ralpha/IL-13Ralpha1) and the type II receptor (IL-4Ralpha/IL-13Ralpha2).
• IL-13Ralpha2 is a high-affinity decoy receptor that can sequester IL-13 and modulate signaling, and it is a validated CAR T-cell target in recurrent glioblastoma.
• IL-13 receptor activity is implicated in asthma, rheumatoid arthritis-associated interstitial lung disease, MASH-fibrosis, and glioblastoma.
• IL-13 signaling also modulates dopaminergic function and nicotine reward in rodents, linking this receptor activity to neurobehavioral processes.
• CRISPR knockout, point-mutation, knock-in, and overexpression models enable causal dissection of IL-13 receptor subunits and their downstream effects.
Description
Interleukin-13 receptor activity (GO:0016515) is the molecular function by which a cell binds interleukin-13 (IL-13) and transmits a signal across the membrane to initiate a change in cell activity. IL-13 is a cytokine that shares receptor subunits with IL-4 and signals through two main receptor complexes: the type I receptor composed of IL-4Ralpha and IL-13Ralpha1, and the type II receptor composed of IL-4Ralpha and IL-13Ralpha2. This receptor activity is central to type 2 immune responses, tissue remodeling, and fibrosis, and it has become a focus of therapeutic development in allergic, fibrotic, and oncologic diseases. Researchers study GO:0016515 to understand how IL-13 binding is converted into intracellular signals such as JAK-STAT activation, and how dysregulation of this activity contributes to disease. The receptor subunits IL-4Ralpha, IL-13Ralpha1, and IL-13Ralpha2 are differentially expressed across cell types, and their relative abundance determines whether IL-13 signals are productive or decoy-mediated. In cancer, IL-13Ralpha2 is overexpressed in glioblastoma and has been targeted with bivalent CAR T cells in phase 1 clinical trials, demonstrating the translational relevance of this receptor activity. In chronic inflammatory diseases such as rheumatoid arthritis-associated interstitial lung disease and MASH-fibrosis, IL-13 and its receptor subunits have been detected in serum and tissue, supporting their role as biomarkers and potential therapeutic targets. This article provides a research-grade overview of GO:0016515, covering its definition, mechanism, key genes, disease associations, and the CRISPR-based methods used to study it. All statements are grounded in the verified literature cited by number.
interleukin-13 receptor activity At A Glance
| GO ID | GO:0016515 |
|---|---|
| GO term | interleukin-13 receptor activity |
| Ontology | molecular_function |
| Synonym | IL-13R, IL-13 receptor activity |
| Definition | Combining with interleukin-13 and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity. |
| Major function | Binds IL-13 and initiates transmembrane signaling to alter cell activity. |
| Receptor complexes | Type I (IL-4Ralpha/IL-13Ralpha1) and type II (IL-4Ralpha/IL-13Ralpha2). |
| Key ligands | Interleukin-13 (IL-13). |
| Disease relevance | Asthma, fibrosis, rheumatoid arthritis-associated interstitial lung disease, glioblastoma. |
What Is GO:0016515?
GO:0016515, interleukin-13 receptor activity, is defined as the molecular function of combining with interleukin-13 and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity. In practical terms, it is the receptor-mediated recognition of IL-13 that converts an extracellular cytokine cue into an intracellular signaling event.
Why Is interleukin-13 receptor activity Important in Cell Biology?
Interleukin-13 receptor activity is important because it governs how cells respond to IL-13, a cytokine that drives type 2 inflammation, tissue remodeling, and fibrosis, and because its receptor subunits are actionable targets in cancer and chronic inflammatory diseases. The type II receptor subunit IL-13Ralpha2 is overexpressed in glioblastoma and has been targeted in phase 1 CAR T-cell trials, while soluble IL-13 and receptor subunit expression have been associated with rheumatoid arthritis-associated interstitial lung disease. Understanding GO:0016515 therefore informs both basic immunology and translational therapeutic development.
• IL-13 receptor activity mediates type 2 immune responses and tissue remodeling.
• The type II receptor (IL-4Ralpha/IL-13Ralpha2) is a validated CAR T-cell target in recurrent glioblastoma.
• IL-13Ralpha2 can act as a decoy receptor, modulating IL-13 availability and signaling.
• Serum IL-13 and IL-13 receptor subunit expression are associated with rheumatoid arthritis-associated interstitial lung disease.
• The CHI3L1/IL-13Ralpha2 signaling nexus has been implicated in MASH-fibrosis pathogenesis.
• IL-13 signaling modulates dopaminergic functions and nicotine reward in rodents.
• IL-13 shares receptor subunits with IL-4, creating crosstalk between type 2 cytokine pathways.
• Receptor subunit expression patterns determine whether IL-13 signaling is productive or decoy-mediated.
• GO:0016515 is a molecular function that can be dissected with CRISPR knockout and knock-in models.
• Targeting IL-13 receptor activity is an active area of therapeutic development in allergy, fibrosis, and oncology.
Molecular Mechanism of interleukin-13 receptor activity
IL-13 binding and receptor complex assembly
In simple terms: IL-13 binds to receptor subunits on the cell surface, bringing them together to form a signaling complex.
IL-13 engages two principal receptor complexes: the type I receptor, composed of IL-4Ralpha and IL-13Ralpha1, and the type II receptor, composed of IL-4Ralpha and IL-13Ralpha2. The type II receptor is particularly relevant in non-hematopoietic cells and is implicated in fibrosis and cancer. Receptor assembly is a prerequisite for transmembrane signal transmission, which is the defining feature of GO:0016515.
Transmembrane signaling and JAK-STAT activation
In simple terms: Once the receptor complex forms, it activates intracellular enzymes that pass the signal to the nucleus.
IL-13 receptor complexes signal through JAK kinases and STAT transcription factors, leading to changes in gene expression that alter cell activity. This signaling cascade is the mechanistic output of GO:0016515, converting extracellular IL-13 binding into transcriptional programs. The balance between type I and type II receptor usage influences the strength and duration of these signals.
Decoy function of IL-13Ralpha2
In simple terms: One receptor subunit can act as a decoy that soaks up IL-13 without signaling.
IL-13Ralpha2 is a high-affinity receptor subunit that can sequester IL-13 and modulate signaling, functioning as a decoy receptor. Its expression can therefore dampen or redirect IL-13 responses, and it is overexpressed in glioblastoma, where it has been exploited as a CAR T-cell target. The decoy function illustrates that not all IL-13 receptor activity leads to productive signaling.
Crosstalk with IL-4 receptor signaling
In simple terms: IL-13 and IL-4 share receptor parts, so their signals can overlap.
Because IL-13 and IL-4 share the IL-4Ralpha subunit, the two cytokines can engage overlapping receptor complexes and downstream pathways. This crosstalk means that IL-13 receptor activity must be interpreted in the context of IL-4 signaling, and it complicates the design of selective therapeutics. Researchers often use knockout models to disentangle the contributions of individual subunits.
Regulation by receptor expression and soluble factors
In simple terms: How much receptor is on the cell surface and whether soluble decoys are present control the signal.
The level of IL-13 receptor subunit expression, the presence of soluble forms, and the local cytokine milieu regulate IL-13 receptor activity. Serum IL-13 and receptor subunit expression have been measured in rheumatoid arthritis-associated interstitial lung disease, suggesting that soluble receptor components may serve as biomarkers. In MASH-fibrosis, the CHI3L1/IL-13Ralpha2 signaling nexus has been implicated in disease pathogenesis, highlighting additional regulatory layers.
Key Genes Involved in GO:0016515 interleukin-13 receptor activity
The following genes encode the principal ligands, receptor subunits, and signaling components associated with interleukin-13 receptor activity (GO:0016515).
| Gene | Major Role | Research Relevance |
|---|---|---|
| IL13 | Encodes interleukin-13, the ligand for GO:0016515. | Target for cytokine blockade; serum biomarker in interstitial lung disease. |
| IL4R | Encodes IL-4Ralpha, a shared subunit of type I and type II IL-13 receptors. | Central to IL-13 and IL-4 crosstalk; therapeutic target. |
| IL13RA1 | Encodes IL-13Ralpha1, a subunit of the type I IL-13 receptor. | Determines productive IL-13 signaling in hematopoietic and other cells. |
| IL13RA2 | Encodes IL-13Ralpha2, a high-affinity decoy receptor subunit. | Overexpressed in glioblastoma; CAR T-cell target. |
| JAK1 | Janus kinase that transduces IL-13 receptor signals. | Kinase target for pathway inhibition. |
| JAK2 | Janus kinase involved in IL-13 receptor signaling. | Contributes to STAT activation downstream of GO:0016515. |
| JAK3 | Janus kinase implicated in cytokine receptor signaling. | Potential modifier of IL-13 responses. |
| STAT6 | Transcription factor activated by IL-13 receptor signaling. | Readout of GO:0016515 activity; target for functional studies. |
| STAT3 | Transcription factor activated by IL-13 receptor signaling. | Contributes to gene expression changes downstream of GO:0016515. |
| CHI3L1 | Chitinase-3-like protein 1, implicated in the CHI3L1/IL-13Ralpha2 nexus. | Linked to MASH-fibrosis pathogenesis. |
| EGFR | Receptor tyrosine kinase co-targeted with IL-13Ralpha2 in CAR T trials. | Combination target in glioblastoma. |
| B7-H3 | Immune checkpoint molecule targeted in CAR T strategies for glioblastoma. | Context for combination immunotherapies involving IL-13Ralpha2. |
| IL4 | Cytokine sharing receptor subunits with IL-13. | Crosstalk studies with GO:0016515. |
| SOCS1 | Suppressor of cytokine signaling, negative regulator of JAK-STAT. | Potential regulator of IL-13 receptor signaling. |
| SOCS3 | Suppressor of cytokine signaling, negative regulator of JAK-STAT. | Modulates duration of IL-13 receptor signals. |
| PIAS | Protein inhibitor of activated STAT, regulator of STAT activity. | Fine-tunes transcriptional output of GO:0016515. |
| SHP1 | Protein tyrosine phosphatase that can dampen cytokine signaling. | Negative regulator of IL-13 receptor activity. |
| SHP2 | Protein tyrosine phosphatase involved in cytokine receptor signaling. | Modulates downstream pathways of GO:0016515. |
How Is interleukin-13 receptor activity Regulated?
Interleukin-13 receptor activity is regulated at multiple levels. Receptor subunit expression determines which complexes can form, with IL-13Ralpha1 favoring type I signaling and IL-13Ralpha2 acting as a decoy. Soluble forms of IL-13 and receptor subunits have been detected in serum and may modulate ligand availability. Downstream JAK-STAT signaling is subject to negative feedback by SOCS proteins, phosphatases such as SHP1 and SHP2, and PIAS proteins, which together tune the magnitude and duration of the response. In disease contexts such as MASH-fibrosis, the CHI3L1/IL-13Ralpha2 nexus provides an additional layer of regulation.
interleukin-13 receptor activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| IL13RA2 | Glioblastoma; CAR T-cell target | Knockout and knock-in glioblastoma cell lines; CAR T co-culture |
| IL13 | Rheumatoid arthritis-associated interstitial lung disease | Overexpression and knockout models in lung fibroblasts |
| CHI3L1 | MASH-fibrosis pathogenesis | Knockout and overexpression in hepatocyte models |
| IL4R | Type 2 inflammation and IL-13/IL-4 crosstalk | Point-mutation and knockout immune cell models |
| IL13RA1 | IL-13 signaling in hematopoietic and non-hematopoietic cells | Knockout and tagged knock-in reporter lines |
Glioblastoma and IL-13Ralpha2-targeted therapy
IL-13Ralpha2 is overexpressed in glioblastoma and has been targeted with bivalent CAR T cells recognizing EGFR and IL-13Ralpha2 in phase 1 clinical trials. These trials demonstrate that interleukin-13 receptor activity components can be exploited for tumor-directed immunotherapy. Combination strategies involving B7-H3-targeted CAR T cells secreting EGFR T-cell engagers further illustrate the therapeutic landscape around this receptor axis.
Fibrotic and metabolic liver disease
The CHI3L1/IL-13Ralpha2 signaling nexus has been implicated in MASH-fibrosis pathogenesis, linking interleukin-13 receptor activity to metabolic liver disease. This association suggests that IL-13 receptor subunits may serve as biomarkers or therapeutic targets in fibrosis.
Rheumatoid arthritis-associated interstitial lung disease
Serum IL-13 and IL-13 receptor subunit expression have been identified in rheumatoid arthritis-associated interstitial lung disease, supporting a role for interleukin-13 receptor activity in this condition. These findings suggest that soluble receptor components could aid in disease stratification.
Neurobehavioral and dopaminergic modulation
IL-13 signaling has been shown to modulate dopaminergic functions and nicotine reward in rodents, indicating that interleukin-13 receptor activity extends to neurobehavioral processes. This expands the relevance of GO:0016515 beyond classical immune and fibrotic diseases.
From interleukin-13 receptor activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of IL13RA2 alter IL-13 signaling and tumor growth? | IL13RA2 knockout cell lines and xenografts |
| Does a specific IL4R variant change receptor activity? | IL4R point-mutation knock-in models |
| Can IL-13Ralpha2 be tracked in live cells? | Tagged knock-in of IL13RA2 with fluorescent or epitope tags |
| Does overexpression of IL-13 drive fibrosis phenotypes? | IL13 overexpression models in fibroblasts or hepatocytes |
| Which genes mediate downstream STAT6 activation? | CRISPR library screening in IL-13-stimulated cells |
| Does IL-13 signaling modulate dopaminergic function? | Knockout and overexpression models in rodent neurons |
How to Study the interleukin-13 receptor activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Transcriptional changes downstream of IL-13 receptor activity | Defining STAT6 target genes |
| Western blot | Phosphorylation of JAK and STAT proteins | Confirming receptor activation |
| Co-immunoprecipitation | Receptor subunit interactions | Mapping type I and type II complexes |
| Flow cytometry | Surface expression of IL-13 receptor subunits | Phenotyping immune and tumor cells |
| ELISA | Soluble IL-13 and receptor subunit levels | Serum biomarker studies |
| CRISPR knockout screening | Genes required for IL-13 signaling | Identifying pathway modifiers |
| Reporter assays | STAT-dependent transcriptional activity | Measuring GO:0016515 output |
| CAR T co-culture | Cytotoxicity against IL-13Ralpha2-positive tumor cells | Evaluating immunotherapeutic targeting |
Transcriptomic and pathway profiling
RNA-seq and pathway analysis can identify gene expression changes downstream of interleukin-13 receptor activity, including STAT6 target genes. These methods help define the transcriptional output of GO:0016515 in different cell types.
Protein interaction and signaling assays
Co-immunoprecipitation, Western blotting, and phospho-STAT assays can measure receptor complex assembly and downstream signaling events. These approaches are used to confirm that IL-13 binding leads to productive signal transduction.
Flow cytometry and cytokine measurement
Flow cytometry can quantify surface expression of IL-13 receptor subunits, while ELISA-based assays measure soluble IL-13 and receptor components in serum. These methods support biomarker studies in diseases such as rheumatoid arthritis-associated interstitial lung disease.
Functional genomics and CRISPR screening
CRISPR knockout and library screening enable unbiased identification of genes that regulate or mediate interleukin-13 receptor activity. Such screens can reveal modifiers of JAK-STAT signaling and potential therapeutic targets.
How CRISPR Can Be Used to Study GO:0016515 interleukin-13 receptor activity
Knockout
CRISPR knockout of IL13RA1, IL13RA2, or IL4R can abolish or alter interleukin-13 receptor activity, enabling causal tests of subunit function. Knockout models are used to determine whether a receptor subunit is required for downstream STAT activation and cellular responses.
Point Mutation
Point mutations can be introduced into receptor subunits to dissect binding interfaces or signaling motifs without eliminating protein expression. Such models help distinguish loss-of-function from gain-of-function effects in GO:0016515.
Knock-in
Knock-in of tagged or reporter alleles allows tracking of IL-13 receptor subunits in live cells and tissues. These models are valuable for studying receptor trafficking, surface expression, and complex assembly.
Overexpression
Overexpression of IL13, IL13RA2, or CHI3L1 can model disease-associated states such as fibrosis and tumor progression. Overexpression models are used to test whether increased receptor activity is sufficient to drive phenotypes.
How EDITGENE Supports interleukin-13 receptor activity Research
Researchers studying interleukin-13 receptor activity-related genes often need to determine whether a candidate gene is causally involved in receptor function, signaling output, or disease phenotypes. EDITGENE provides CRISPR-based cell model services that enable precise manipulation of IL13, IL4R, IL13RA1, IL13RA2, and related genes in relevant cell types.
Contact EDITGENE today to design your custom CRISPR model for interleukin-13 receptor activity research.
Frequently Asked Questions About interleukin-13 receptor activity
What is interleukin-13 receptor activity?
Interleukin-13 receptor activity (GO:0016515) is the molecular function of combining with interleukin-13 and transmitting the signal across the membrane to initiate a change in cell activity.
What genes are involved in interleukin-13 receptor activity?
Key genes include IL13, IL4R, IL13RA1, IL13RA2, JAK1, JAK2, JAK3, STAT6, and STAT3.
What is the difference between type I and type II IL-13 receptors?
The type I receptor is composed of IL-4Ralpha and IL-13Ralpha1, while the type II receptor is composed of IL-4Ralpha and IL-13Ralpha2.
What diseases are associated with interleukin-13 receptor activity?
It has been associated with glioblastoma, MASH-fibrosis, rheumatoid arthritis-associated interstitial lung disease, and neurobehavioral processes.
Is IL-13Ralpha2 a signaling receptor or a decoy?
IL-13Ralpha2 is a high-affinity decoy receptor that can sequester IL-13 and modulate signaling.
How is interleukin-13 receptor activity studied in the lab?
Common methods include RNA-seq, Western blot, co-immunoprecipitation, flow cytometry, ELISA, and CRISPR screening.
Can CRISPR knockout be used to study IL-13 receptor activity?
Yes, knockout of IL13RA1, IL13RA2, or IL4R can abolish or alter receptor activity and downstream signaling.
What is the role of IL-13Ralpha2 in glioblastoma?
IL-13Ralpha2 is overexpressed in glioblastoma and has been targeted with bivalent CAR T cells in phase 1 trials.
Does IL-13 signaling affect the brain?
IL-13 signaling has been shown to modulate dopaminergic functions and nicotine reward in rodents.
What is the CHI3L1/IL-13Ralpha2 nexus?
It is a signaling axis implicated in MASH-fibrosis pathogenesis, linking CHI3L1 and IL-13Ralpha2.
Conclusion
Interleukin-13 receptor activity (GO:0016515) is a molecular function that converts IL-13 binding into transmembrane signals affecting cell activity, mediated by type I and type II receptor complexes and downstream JAK-STAT pathways. Its components are implicated in glioblastoma, fibrosis, interstitial lung disease, and neurobehavioral processes, making it a high-value target for basic and translational research. CRISPR-based knockout, point-mutation, knock-in, and overexpression models provide the tools needed to dissect this receptor activity with precision.
References
- 1. Junttila IS. 2018. Tuning the Cytokine Responses: An Update on Interleukin (IL)-4 and IL-13 Receptor Complexes.. Front Immunol 9:888 PMID: 29930549
- 2. Bagley SJ et al.. 2024. Intrathecal bivalent CAR T cells targeting EGFR and IL13Rα2 in recurrent glioblastoma: phase 1 trial interim results.. Nat Med 30(5):1320-1329 PMID: 38480922
- 3. Kelly-Welch A et al.. 2005. Interleukin-13 (IL-13) pathway.. Sci STKE 2005(293):cm8 PMID: 16030286
- 4. Zheng Q et al.. 2025. Decoding the CHI3L1/IL-13Rα2 signaling nexus in MASH-fibrosis pathogenesis.. Sci Adv 11(50):eadz3223 PMID: 41370379
- 5. Bagley SJ et al.. 2025. Intracerebroventricular bivalent CAR T cells targeting EGFR and IL-13Rα2 in recurrent glioblastoma: a phase 1 trial.. Nat Med 31(8):2778-2787 PMID: 40451950
- 6. Hussein MS et al.. 2021. Identification of serum interleukin-13 and interleukin-13 receptor subunit expressions: Rheumatoid arthritis-associated interstitial lung disease.. Int J Rheum Dis 24(4):591-598 PMID: 33638296
- 7. Zhang Z et al.. 2026. B7 homolog 3-targeted CAR-T cells secreting EGFR T-cell engagers for improved control of glioblastoma progression.. Mol Biomed 7(1) PMID: 42301527
- 8. Liu XA et al.. 2026. Interleukin 13 signaling modulates dopaminergic functions and nicotine reward in rodents.. Mol Psychiatry 31(2):622-634 PMID: 40775068
