GO:0071348 cellular response to interleukin-11: Signaling Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0071348 (cellular response to interleukin-11) describes all cellular changes triggered by the cytokine interleukin-11 (IL-11), including altered gene expression, secretion, movement and enzyme production.
• IL-11 signals through a receptor complex of IL11RA and gp130, activating JAK/STAT3, ERK and SRC-YAP cascades that drive fibrosis, inflammation and cancer progression.
• IL-11 is a pivotal driver of cardiovascular fibrosis and is being pursued as a therapeutic target in fibrotic and inflammatory diseases.
• IL-11 also regulates bone-fat homeostasis in response to mechanical loading, linking the cellular response to skeletal mechanobiology.
• Therapeutic IL-11 administration can cause acute left ventricular dysfunction, underscoring the need for precise, cell-type-specific studies of this response.
• CRISPR knockout, point-mutation, knock-in and overexpression models are essential to dissect the causal roles of IL-11 pathway genes in disease.
Description
The Gene Ontology term GO:0071348, cellular response to interleukin-11, defines the set of processes by which a cell changes its state or activity in response to an interleukin-11 (IL-11) stimulus. IL-11 is a pleiotropic cytokine of the IL-6 family that acts on a wide range of cell types, including fibroblasts, cardiomyocytes, epithelial cells and osteoblasts, to modulate gene expression, secretion, movement and enzyme production. Because IL-11 is increasingly recognized as a disease gene and therapeutic target, understanding the cellular response to IL-11 is central to fibrosis, inflammation and cancer research. The response is initiated when IL-11 binds its specific alpha receptor IL11RA, which then recruits the shared signal-transducing subunit gp130 (IL6ST) to form a functional receptor complex. This complex activates intracellular kinases, most notably JAK family kinases, which phosphorylate STAT3 and other effectors to reprogram transcription. The term therefore encompasses receptor-proximal signaling, transcriptional reprogramming, and downstream phenotypic changes such as extracellular matrix production, cell dedifferentiation and altered proliferation. Researchers study GO:0071348 to identify the genes and mechanisms that convert a transient cytokine cue into persistent pathological states, and to evaluate whether blocking or enhancing specific nodes can reverse disease.
cellular response to interleukin-11 At A Glance
| GO ID | GO:0071348 |
|---|---|
| GO term | cellular response to interleukin-11 |
| Ontology | biological_process |
| Synonym | cellular response to IL-11 |
| Definition | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interleukin-11 stimulus. |
| Major function | Transduces IL-11 cytokine signals into transcriptional and phenotypic changes, including fibrosis, inflammation and cell dedifferentiation. |
| Key receptor complex | IL11RA (ligand-specific alpha subunit) and gp130/IL6ST (shared signal-transducing subunit). |
| Major downstream pathways | JAK/STAT3, ERK/MAPK, SRC-YAP and PI3K-AKT signaling. |
| Representative cell types | Fibroblasts, cardiomyocytes, epithelial cells, osteoblasts and hematopoietic cells. |
What Is GO:0071348?
In our own words, GO:0071348 (cellular response to interleukin-11) is the biological process comprising any change in a cell's state or activity that results from an interleukin-11 stimulus. This includes changes in movement, secretion, enzyme production and gene expression, and it is synonymous with the cellular response to IL-11.
Why Is cellular response to interleukin-11 Important in Cell Biology?
GO:0071348 is important because the cellular response to IL-11 is a central node in fibrotic, inflammatory and malignant disease, and because IL-11 is now considered a disease gene and therapeutic target. Blocking IL-11 signaling reduces cardiovascular fibrosis in preclinical models, while therapeutic IL-11 administration can cause acute left ventricular dysfunction, illustrating that the response must be tightly controlled. The term also connects cytokine biology to bone-fat homeostasis and mechanical loading, broadening its relevance beyond fibrosis. For researchers, GO:0071348 provides a structured framework to annotate and interpret experiments that perturb IL-11 signaling, from receptor binding to downstream transcriptional outputs.
• IL-11 signaling is a crucial determinant of cardiovascular fibrosis and heart failure pathology.
• IL-11 is recognized as a disease gene and therapeutic target across fibrotic and inflammatory conditions.
• The cellular response to IL-11 regulates bone-fat linkage in response to mechanical loading.
• Therapeutic IL-11 can cause acute left ventricular dysfunction, highlighting dose- and context-dependent effects.
• IL-11 belongs to the IL-6 family of cytokines and shares the gp130 signal-transducing subunit.
• TGF-beta and RAS signaling can cooperate with IL-11-related programs to drive metastasis.
• IL-11-associated pathways intersect with regenerative programs such as Ascl2-dependent intestinal stem cell dedifferentiation.
• The response is relevant to cancer, fibrosis, inflammation and regenerative medicine.
• CRISPR-based perturbation of IL-11 pathway genes enables causal testing of therapeutic hypotheses.
• Understanding GO:0071348 supports biomarker discovery and target validation for anti-fibrotic and anti-cancer therapies.
What Happens During cellular response to interleukin-11?
IL-11 binding and receptor complex assembly
In simple terms: IL-11 docks onto a specific receptor on the cell surface, which then recruits a shared signaling partner to start the message.
The cellular response to IL-11 begins when IL-11 binds the ligand-specific alpha receptor IL11RA, which then recruits the shared signal-transducing subunit gp130 (IL6ST) to form a functional receptor complex. This assembly is the committed step that converts an extracellular cytokine cue into an intracellular signal, and it is the point at which IL-11 signaling can be selectively blocked relative to other IL-6 family cytokines.
Activation of JAK/STAT3 signaling
In simple terms: Once the receptor is assembled, enzymes called JAKs tag STAT3, which then travels to the nucleus to switch genes on or off.
Receptor complex formation activates JAK family kinases, which phosphorylate STAT3 and other downstream effectors. Phosphorylated STAT3 dimerizes and translocates to the nucleus, where it reprograms transcription of genes controlling fibrosis, inflammation, proliferation and extracellular matrix production. This JAK/STAT3 axis is a defining feature of the cellular response to IL-11 and a major focus of therapeutic targeting.
ERK/MAPK and SRC-YAP effector cascades
In simple terms: IL-11 also flips other switches inside the cell, including growth and mechanical-stress pathways.
Beyond STAT3, IL-11 signaling engages ERK/MAPK and SRC-YAP cascades that contribute to fibroblast activation, proliferation and matrix remodeling. These non-STAT3 arms help explain why IL-11 responses are pleiotropic and context-dependent, and they provide additional nodes for pharmacological or genetic intervention.
Transcriptional reprogramming and phenotypic output
In simple terms: The final result is a changed cell: it makes different proteins, secretes different factors and may move or divide differently.
The integrated output of the cellular response to IL-11 is a change in gene expression, secretion, enzyme production and cell movement. In fibroblasts and cardiomyocytes, this manifests as increased extracellular matrix deposition and fibrosis; in epithelial and stem cell contexts, it can drive dedifferentiation and regenerative programs. TGF-beta and RAS signaling can cooperate with IL-11-related programs to promote metastasis, illustrating how the response integrates with other oncogenic pathways.
Bone-fat and mechanobiology context
In simple terms: IL-11 also helps bones and fat tissue communicate when the body is mechanically loaded.
The cellular response to IL-11 participates in bone-fat linkage in response to mechanical loading, linking cytokine signaling to skeletal mechanobiology. This context expands the physiological relevance of GO:0071348 beyond fibrosis and cancer to bone and metabolic homeostasis.
Key Genes Involved in GO:0071348 cellular response to interleukin-11
The following genes and proteins are central to the cellular response to interleukin-11 (GO:0071348), spanning ligand, receptor, kinase and downstream effector functions.
| Gene | Major Role | Research Relevance |
|---|---|---|
| IL11 | Ligand cytokine that initiates the cellular response | Core stimulus for GO:0071348; target for anti-fibrotic therapy |
| IL11RA | Ligand-specific alpha receptor for IL-11 | Determines cell-type specificity of the response |
| IL6ST | Shared signal-transducing subunit gp130 | Required for JAK/STAT3 activation downstream of IL-11 |
| JAK1 | Janus kinase that phosphorylates STAT3 | Receptor-proximal kinase in the IL-11 signaling cascade |
| JAK2 | Janus kinase contributing to IL-11 signal transduction | Alternative JAK family kinase in cytokine signaling |
| STAT3 | Transcription factor that reprograms gene expression | Central effector of the cellular response to IL-11 |
| MAPK1 | ERK/MAPK effector kinase | Mediates non-STAT3 arms of IL-11 signaling |
| MAPK3 | ERK/MAPK effector kinase | Contributes to proliferation and matrix remodeling |
| SRC | Non-receptor tyrosine kinase | Links IL-11 signaling to SRC-YAP cascades |
| YAP1 | Transcriptional co-activator in mechanotransduction | Mediates SRC-YAP arm of IL-11 response |
| TGFB1 | Profibrotic cytokine that cooperates with IL-11 | Co-drives metastasis and fibrosis programs |
| ASCL2 | Transcription factor driving dedifferentiation | Links regenerative programs to cytokine signaling |
| COL1A1 | Extracellular matrix component | Readout of fibrotic output of IL-11 response |
| COL3A1 | Extracellular matrix component | Readout of fibrotic output of IL-11 response |
| ACTA2 | Smooth muscle actin, myofibroblast marker | Marker of fibroblast activation downstream of IL-11 |
| IL6 | Related IL-6 family cytokine | Context for shared gp130 signaling |
| LIF | Related IL-6 family cytokine | Context for shared gp130 signaling |
How Is cellular response to interleukin-11 Regulated?
The cellular response to IL-11 is regulated at multiple levels. Receptor availability is controlled by expression of IL11RA and the shared subunit gp130 (IL6ST), which determines which cells can respond. Intracellularly, JAK-mediated phosphorylation of STAT3 is balanced by negative regulators such as SOCS proteins and phosphatases, although specific regulators in the IL-11 context require further study. Crosstalk with TGF-beta and RAS signaling can amplify or redirect the response toward metastasis and fibrosis. In bone and fat tissue, mechanical loading modulates IL-11 signaling as part of bone-fat linkage. Therapeutic administration of IL-11 can cause acute left ventricular dysfunction, indicating that the magnitude and duration of the response are physiologically constrained.
cellular response to interleukin-11 and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| IL11 | Cardiovascular fibrosis and heart failure | IL11 knockout or overexpression in cardiac fibroblasts |
| IL11RA | Fibrotic and inflammatory disease | IL11RA knockout cell models to block the response |
| STAT3 | Cancer and fibrosis | STAT3 point-mutation or knockout to dissect downstream signaling |
| TGFB1 | Metastasis and fibrosis | TGFB1/IL11 co-perturbation models |
| ASCL2 | Intestinal regeneration | ASCL2 knockout or overexpression in intestinal organoids |
Cardiovascular fibrosis and heart failure
IL-11 is a crucial determinant of cardiovascular fibrosis, and its cellular response drives fibroblast activation and extracellular matrix deposition in the heart. Blocking IL-11 signaling reduces fibrosis in preclinical models, while therapeutic IL-11 administration can cause acute left ventricular dysfunction, highlighting the need for precise modulation. These findings position GO:0071348 as a central mechanism in cardiac fibrotic disease.
Cancer and metastasis
IL-11 signaling is recognized as a disease gene and therapeutic target in cancer, where it promotes proliferation, survival and metastasis. TGF-beta and RAS signaling jointly unmask primed enhancers to drive metastasis, and IL-11-related programs can cooperate in this process. The cellular response to IL-11 therefore represents a tractable axis for anti-metastatic strategies.
Bone and metabolic homeostasis
IL-11 participates in bone-fat linkage in response to mechanical loading, connecting the cellular response to skeletal and metabolic physiology. Dysregulation of this response may contribute to bone loss or altered marrow adiposity, although the precise disease associations require further investigation.
Inflammation and regeneration
As an IL-6 family cytokine, IL-11 modulates inflammatory and regenerative programs, including Ascl2-dependent intestinal stem cell dedifferentiation. The cellular response to IL-11 can therefore influence tissue repair and regeneration, with context-dependent beneficial or detrimental effects.
From cellular response to interleukin-11-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does IL11 loss block fibrosis? | IL11 knockout fibroblasts or cardiomyocytes |
| Does IL11RA mediate the response? | IL11RA knockout cell lines |
| Which STAT3 residues are required? | STAT3 point-mutation knock-in |
| Can we track receptor complex formation? | Tagged knock-in of IL11RA or IL6ST |
| Does IL-11 overexpression drive disease? | IL11 overexpression models |
| Which genes mediate the response? | CRISPR library screening in IL-11-treated cells |
How to Study the cellular response to interleukin-11 Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Global gene expression changes | Defining the transcriptional output of IL-11 response |
| Phosphoproteomics | Kinase activation and signaling nodes | Mapping JAK/STAT3, ERK and SRC activation |
| Immunoblotting | Protein phosphorylation and abundance | Validating pathway activation |
| Live-cell imaging | Receptor assembly and STAT3 translocation | Spatiotemporal dynamics of the response |
| Reporter assays | Transcriptional activity | Quantifying pathway output |
| Proliferation and migration assays | Cell behavior changes | Phenotypic readout of IL-11 response |
| Collagen deposition assays | Extracellular matrix production | Fibrosis modeling |
| CRISPR library screening | Gene dependencies | Identifying regulators of the response |
Transcriptomic profiling of the IL-11 response
RNA-seq after IL-11 stimulation identifies the gene expression changes that define GO:0071348, including extracellular matrix genes, inflammatory mediators and transcription factors. Comparing wild-type and knockout cells reveals which genes are causally downstream of IL11RA, gp130 and STAT3.
Phosphoproteomics and signaling assays
Phosphoproteomics and immunoblotting for phosphorylated STAT3, ERK and SRC measure the activation of receptor-proximal and distal signaling arms in the cellular response to IL-11. These methods quantify pathway engagement and can be combined with kinase inhibitors to map dependencies.
Imaging and reporter assays
Live-cell imaging of tagged receptors and STAT3 nuclear translocation, together with transcriptional reporters, visualizes the spatiotemporal dynamics of the IL-11 response. These approaches help distinguish transient from sustained signaling in different cell types.
Functional and phenotypic readouts
Proliferation, migration, collagen deposition and differentiation assays translate molecular signaling into the phenotypic outputs of GO:0071348, such as fibrosis and dedifferentiation. Combining these readouts with genetic perturbation establishes causality.
How CRISPR Can Be Used to Study GO:0071348 cellular response to interleukin-11
Knockout
CRISPR knockout of IL11, IL11RA, IL6ST or STAT3 abolishes or attenuates the cellular response to IL-11, providing causal evidence for their roles in fibrosis and inflammation. Knockout models are widely used to test whether blocking the pathway reverses disease phenotypes.
Point Mutation
Point-mutation knock-in of specific phosphorylation sites or binding residues in STAT3, gp130 or IL11RA allows precise dissection of which molecular features are required for the response. Such models distinguish signaling arms and reveal structure-function relationships.
Knock-in
Tagged knock-in of IL11RA, IL6ST or STAT3 enables tracking of receptor complex assembly, trafficking and nuclear translocation in live cells. Knock-in reporters can also quantify transcriptional output of the response.
Overexpression
Overexpression of IL11 or constitutively active pathway components drives fibrosis and left ventricular dysfunction in preclinical models, mimicking pathological activation of GO:0071348. Overexpression systems are useful for testing therapeutic interventions that aim to dampen the response.
How EDITGENE Supports cellular response to interleukin-11 Research
Researchers studying cellular response to interleukin-11-related genes often need to determine whether a candidate gene is causally involved in the response or merely correlated with it. EDITGENE provides the CRISPR tools and bioinformatics support required to move from association to causation in IL-11 pathway research.
Contact EDITGENE today to design your custom CRISPR model for cellular response to interleukin-11 research.
Frequently Asked Questions About cellular response to interleukin-11
What is GO:0071348 cellular response to interleukin-11?
GO:0071348 is a Gene Ontology biological process term describing any change in a cell's state or activity, such as movement, secretion, enzyme production or gene expression, that results from an interleukin-11 stimulus.
What genes are involved in the cellular response to interleukin-11?
Key genes include IL11, IL11RA, IL6ST (gp130), JAK1, JAK2, STAT3, MAPK1, MAPK3, SRC and YAP1, which together transduce and execute the response.
How does IL-11 signal inside the cell?
IL-11 binds IL11RA, which recruits gp130 to activate JAK kinases, leading to STAT3 phosphorylation and transcriptional reprogramming, as well as ERK and SRC-YAP signaling.
Why is IL-11 important in fibrosis?
IL-11 is a crucial determinant of cardiovascular fibrosis, and blocking its signaling reduces fibrotic remodeling in preclinical models.
Can IL-11 therapy cause heart problems?
Yes, therapeutic IL-11 administration has been shown to cause acute left ventricular dysfunction, indicating that the response must be carefully controlled.
What is the role of IL-11 in bone and fat?
IL-11 participates in bone-fat linkage in response to mechanical loading, connecting cytokine signaling to skeletal and metabolic homeostasis.
How can I study the cellular response to IL-11 in the lab?
Common approaches include RNA-seq, phosphoproteomics, immunoblotting, live-cell imaging, reporter assays and CRISPR-based perturbation of pathway genes.
What CRISPR models are useful for IL-11 research?
Knockout, point-mutation, knock-in, tagged knock-in and overexpression models of IL11, IL11RA, IL6ST and STAT3 are widely used to dissect the pathway.
Is IL-11 a therapeutic target?
IL-11 is recognized as a disease gene and therapeutic target, particularly in fibrotic and inflammatory diseases and cancer.
How does IL-11 relate to cancer metastasis?
IL-11 signaling can cooperate with TGF-beta and RAS pathways to drive metastasis, making it a candidate target for anti-metastatic strategies.
Conclusion
GO:0071348 (cellular response to interleukin-11) captures a central cytokine signaling process that shapes fibrosis, inflammation, cancer and bone-fat homeostasis. Its core mechanism involves IL11RA-gp130 receptor assembly, JAK/STAT3 activation and additional ERK and SRC-YAP cascades that together reprogram cell behavior. Because IL-11 is a validated disease gene and therapeutic target, precise causal studies using CRISPR knockout, point-mutation, knock-in and overexpression models are essential to translate pathway knowledge into safe therapies. EDITGENE supports these efforts with end-to-end cell model generation, screening and bioinformatics services tailored to IL-11 pathway research.
References
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