GO:0071105 response to interleukin-11: Signaling Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0071105 (response to interleukin-11) describes any cellular or organismal change triggered by the cytokine interleukin-11 (IL-11).
• IL-11 signals through the IL-11 receptor alpha (IL11RA) and gp130, activating JAK/STAT, MAPK and other downstream cascades.
• IL-11 is a critical driver of cardiovascular fibrosis and is being pursued as a therapeutic target.
• IL-11 also regulates bone-fat balance in response to mechanical loading and constrains thermogenic capacity of beige adipocytes.
• TGF-beta and RAS signaling can unmask primed enhancers that cooperate with IL-11 to drive metastasis.
• CRISPR knockout, knock-in, point-mutation and overexpression models are essential to dissect IL-11 pathway causality in disease.
Description
Interleukin-11 (IL-11) is a pleiotropic cytokine belonging to the IL-6 family that elicits a wide range of cellular responses, collectively annotated as GO:0071105 response to interleukin-11. This biological process encompasses changes in gene expression, secretion, enzyme production, movement and other activities that occur when a cell or organism encounters an IL-11 stimulus. Since its discovery, IL-11 has been implicated in hematopoiesis, inflammation, fibrosis, bone remodeling and cancer progression. Understanding the precise molecular events triggered by IL-11 is therefore of broad biomedical importance. Recent studies have identified IL-11 as a crucial determinant of cardiovascular fibrosis, a regulator of bone-fat linkage under mechanical loading, and a metabolic constraint on beige adipocyte thermogenesis. Moreover, IL-11 cooperates with TGF-beta and RAS signaling to drive metastatic programs. These findings position GO:0071105 at the intersection of fibrosis, metabolism, oncology and regenerative medicine. Researchers studying this process require robust experimental models, including CRISPR-engineered cell lines and animal models, to determine causality and identify therapeutic vulnerabilities.
response to interleukin-11 At A Glance
| GO ID | GO:0071105 |
|---|---|
| GO term | response to interleukin-11 |
| Ontology | biological_process |
| Synonym | response to IL-11 |
| Definition | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interleukin-11 stimulus. |
| Major function | Mediates cellular responses to the cytokine IL-11, including JAK/STAT activation, gene expression changes, and effects on proliferation, fibrosis, metabolism and metastasis. |
| Key receptor | IL-11 receptor alpha (IL11RA) in complex with gp130 (IL6ST) |
| Downstream pathways | JAK/STAT3, MAPK/ERK, PI3K/AKT |
| Disease relevance | Cardiovascular fibrosis, cancer metastasis, bone-fat imbalance, metabolic dysfunction |
What Is GO:0071105?
GO:0071105 response to interleukin-11 is defined as any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interleukin-11 stimulus. In simpler terms, it is the entire set of cellular reactions that occur after a cell detects IL-11, including activation of signaling cascades, changes in gene transcription, and functional outputs such as proliferation, differentiation or matrix production.
Why Is response to interleukin-11 Important in Cell Biology?
GO:0071105 is critically important because IL-11 signaling is a central node in fibrosis, cancer and metabolic disease, and it represents a tractable therapeutic target. Blocking IL-11 or its receptor has been shown to reduce cardiovascular fibrosis in preclinical models, and IL-11 therapy itself can cause acute left ventricular dysfunction, underscoring the need for precise understanding of this pathway. Furthermore, IL-11 links mechanical loading to bone-fat balance and constrains the thermogenic capacity of beige adipocytes, connecting this GO term to osteoporosis, obesity and energy homeostasis. In oncology, IL-11 cooperates with TGF-beta and RAS to drive metastasis, making it a potential target for anti-metastatic strategies.
• IL-11 is a crucial determinant of cardiovascular fibrosis, and its inhibition reduces fibrosis in animal models.
• IL-11 therapy can cause acute left ventricular dysfunction, highlighting the need to understand its signaling.
• IL-11 mediates bone-fat linkage in response to mechanical loading, affecting skeletal and adipose homeostasis.
• IL-11/IL-11RA signaling constrains sphingolipid metabolism and limits thermogenic capacity of beige adipocytes.
• TGF-beta and RAS jointly unmask primed enhancers that cooperate with IL-11 to drive metastasis.
• IL-11 is a disease gene and therapeutic target across multiple organ systems.
• IL-11 was originally characterized as a hematopoietic cytokine, and its role in blood cell development remains relevant.
• Understanding GO:0071105 enables rational design of inhibitors and biologics targeting IL-11 signaling.
• CRISPR-based models are essential to establish causality of IL-11 pathway components in disease.
• IL-11 signaling intersects with TGF-beta, RAS and metabolic pathways, offering multiple points for therapeutic intervention.
What Happens During response to interleukin-11?
IL-11 binding and receptor complex assembly
In simple terms: IL-11 docks onto its receptor on the cell surface, setting off a chain reaction inside the cell.
The response to interleukin-11 begins when IL-11 binds to the IL-11 receptor alpha chain (IL11RA), which then recruits the shared signal-transducing subunit gp130 (IL6ST) to form a functional signaling complex. This assembly is a prerequisite for downstream activation and is a key step in GO:0071105. The IL-11/IL11RA/gp130 complex is expressed in various cell types, including fibroblasts, osteoblasts, adipocytes and cancer cells, enabling pleiotropic responses.
Activation of JAK/STAT and MAPK cascades
In simple terms: The receptor complex turns on enzymes that carry signals to the nucleus and other parts of the cell.
Upon receptor assembly, Janus kinases (JAKs) associated with gp130 are activated and phosphorylate STAT proteins, particularly STAT3, which translocate to the nucleus to regulate gene expression. In parallel, the MAPK/ERK and PI3K/AKT pathways can be engaged, contributing to changes in proliferation, survival and matrix production. These signaling events are central to the cellular response to IL-11 and are frequently dysregulated in fibrosis and cancer.
Transcriptional reprogramming and enhancer activation
In simple terms: The signal reaches the DNA and switches genes on or off, sometimes with help from other signals.
IL-11 signaling induces transcriptional changes that underlie its biological effects. Recent work has shown that TGF-beta and RAS signaling jointly unmask primed enhancers, which then cooperate with IL-11 to drive a metastatic gene program. This indicates that the response to IL-11 is not isolated but integrates with other pathways to reshape the epigenome and transcriptome. Such transcriptional reprogramming is a hallmark of GO:0071105 in disease contexts.
Metabolic and functional outputs
In simple terms: The cell changes its behavior and metabolism in response to IL-11.
Downstream of transcriptional changes, IL-11 alters cellular metabolism and function. For example, IL-11/IL-11RA signaling constrains sphingolipid metabolism to limit the thermogenic capacity of beige adipocytes. In bone, IL-11 mediates a bone-fat linkage in response to mechanical loading, influencing osteoblast and adipocyte differentiation. These metabolic and functional outputs represent the effector phase of the response to interleukin-11.
Pathological consequences: fibrosis and metastasis
In simple terms: When IL-11 signaling goes wrong, it can cause scarring and help cancer spread.
Excessive or sustained IL-11 signaling drives pathological outcomes. IL-11 is a crucial determinant of cardiovascular fibrosis, and its inhibition reduces fibrosis in preclinical models. However, IL-11 therapy itself can cause acute left ventricular dysfunction, illustrating the need for precise modulation. In cancer, IL-11 cooperates with TGF-beta and RAS to promote metastasis. Thus, the response to interleukin-11 can be protective or harmful depending on context, making it a critical process to study.
Key Genes Involved in GO:0071105 response to interleukin-11
The following genes and proteins are central to the response to interleukin-11 (GO:0071105) and are frequently studied using CRISPR-based approaches.
| Gene | Major Role | Research Relevance |
|---|---|---|
| IL11 | Ligand cytokine that initiates the response | Target for knockout and overexpression to study fibrosis and metastasis |
| IL11RA | Specific receptor alpha chain for IL-11 | Knockout models to block IL-11 signaling; point mutations to dissect binding |
| IL6ST | gp130 shared signal-transducing subunit | Essential for JAK/STAT activation; knockout causes loss of response |
| JAK1 | Janus kinase that phosphorylates STATs | Kinase inhibitor targets; knockout reduces IL-11 signaling |
| JAK2 | Janus kinase involved in cytokine signaling | Contributes to IL-11-induced STAT activation |
| STAT3 | Transcription factor downstream of IL-11 | Key mediator of gene expression; knockout abolishes many IL-11 effects |
| STAT1 | Transcription factor activated by IL-11 | Modulates inflammatory and anti-proliferative responses |
| MAPK1 | ERK2 kinase in MAPK cascade | Mediates proliferative signals downstream of IL-11 |
| MAPK3 | ERK1 kinase in MAPK cascade | Cooperates with MAPK1 in IL-11-induced signaling |
| PIK3CA | Catalytic subunit of PI3K | Activates AKT pathway downstream of IL-11 |
| AKT1 | Serine/threonine kinase | Promotes survival and metabolic changes in response to IL-11 |
| TGFB1 | TGF-beta ligand that cooperates with IL-11 | Jointly unmasks enhancers to drive metastasis |
| KRAS | RAS oncogene that synergizes with IL-11 | Drives metastatic programs with TGF-beta and IL-11 |
| SPHK1 | Sphingosine kinase 1 in sphingolipid metabolism | Regulated by IL-11 to limit thermogenesis |
| CEBPA | Adipogenic transcription factor | Modulated by IL-11 in bone-fat balance |
| PPARG | Master regulator of adipogenesis | Affected by IL-11 signaling in beige adipocytes |
| RUNX2 | Osteoblast differentiation factor | Linked to IL-11 response in mechanical loading |
How Is response to interleukin-11 Regulated?
The response to interleukin-11 is tightly regulated at multiple levels. Receptor availability is controlled by expression of IL11RA and gp130, and soluble forms of IL-11RA can act as decoys. Negative feedback mechanisms include SOCS proteins and phosphatases that dampen JAK/STAT signaling. Additionally, crosstalk with TGF-beta and RAS pathways can amplify or modify the response, as shown by the joint unmasking of primed enhancers. Metabolic status also influences IL-11 signaling; for instance, IL-11/IL-11RA constrains sphingolipid metabolism in beige adipocytes, and this regulation is tied to thermogenic capacity. Mechanical loading regulates IL-11 expression in bone, linking physical forces to bone-fat balance. These layers of regulation ensure context-dependent outcomes of GO:0071105.
response to interleukin-11 and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| IL11 | Cardiovascular fibrosis | IL11 knockout mice or CRISPR knockout in cardiac fibroblasts |
| IL11RA | Fibrosis and inflammation | IL11RA knockout cell lines and mice |
| IL11 | Cancer metastasis | CRISPR knockout in metastatic cancer cell lines with RAS/TGF-beta activation |
| IL11 | Bone-fat imbalance | Conditional knockout in bone or adipose tissue |
| IL11RA | Metabolic dysfunction | Adipocyte-specific knockout or overexpression |
Cardiovascular fibrosis and heart failure
IL-11 is a crucial determinant of cardiovascular fibrosis, and its inhibition reduces fibrosis in preclinical models. However, IL-11 therapy can cause acute left ventricular dysfunction, indicating that both excess and exogenous IL-11 can be detrimental. The response to interleukin-11 in cardiac fibroblasts drives extracellular matrix production, contributing to heart failure. Targeting IL-11 signaling is therefore a promising therapeutic strategy for fibrotic heart disease.
Cancer metastasis
IL-11 cooperates with TGF-beta and RAS signaling to drive metastasis. TGF-beta and RAS jointly unmask primed enhancers that, together with IL-11, promote a metastatic gene program. This places GO:0071105 at the center of metastatic progression in cancers with active RAS and TGF-beta pathways. Inhibiting IL-11 signaling may reduce metastatic burden in such tumors.
Bone and metabolic disorders
IL-11 mediates a bone-fat linkage in response to mechanical loading, influencing the balance between osteogenesis and adipogenesis. Additionally, IL-11/IL-11RA signaling constrains sphingolipid metabolism to limit the thermogenic capacity of beige adipocytes. Dysregulated IL-11 signaling may therefore contribute to osteoporosis, obesity and impaired energy expenditure. Understanding GO:0071105 in these contexts could reveal new therapeutic avenues for metabolic bone diseases.
From response to interleukin-11-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does IL-11 drive cardiac fibrosis? | IL11 or IL11RA knockout mice subjected to fibrosis-inducing stimuli |
| What is the role of IL-11 in metastasis? | CRISPR knockout of IL11 in RAS/TGF-beta-driven cancer cells followed by metastasis assays |
| How does IL-11 affect bone-fat balance? | Conditional knockout of IL11 in osteoblasts or adipocytes under mechanical loading |
| Does IL-11 regulate thermogenesis? | Adipocyte-specific IL11RA knockout or IL-11 overexpression in beige adipocytes |
| What are the downstream effectors of IL-11? | STAT3 knockout or point-mutation knock-in cell lines |
| Can IL-11 signaling be targeted therapeutically? | Knock-in of tagged IL-11 for tracking and drug testing |
How to Study the response to interleukin-11 Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Global gene expression changes | Identify transcriptional programs induced by IL-11 |
| Phosphoproteomics | Phosphorylation of signaling proteins | Map JAK/STAT and MAPK activation |
| CRISPR knockout screens | Genes required for IL-11 response | Discover novel regulators and drug targets |
| Luciferase reporter assays | STAT3 or enhancer activity | Monitor IL-11 signaling in real time |
| Western blot | Protein levels and phosphorylation | Validate specific pathway components |
| Immunofluorescence | Subcellular localization | Track STAT3 nuclear translocation |
| Metabolic assays | Sphingolipid metabolism and thermogenesis | Study IL-11 effects on adipocytes |
| Mechanical loading models | Bone-fat balance in vivo | Assess IL-11 response to physical forces |
Transcriptomic profiling (RNA-seq)
RNA sequencing is widely used to measure global gene expression changes in response to IL-11 stimulation. This method can identify transcriptional programs activated by GO:0071105, including those involving TGF-beta and RAS cooperation. Comparing wild-type and CRISPR knockout cells reveals specific pathways dependent on IL-11 signaling.
Proteomic and phosphoproteomic analysis
Mass spectrometry-based proteomics can quantify protein abundance and phosphorylation events downstream of IL-11 receptor activation. This approach helps map the JAK/STAT and MAPK cascades triggered by IL-11. Phosphoproteomics is particularly useful for identifying immediate signaling nodes in GO:0071105.
CRISPR screening and functional genomics
Genome-wide CRISPR knockout screens can identify genes that modulate the response to IL-11, such as those required for STAT3 activation or metabolic reprogramming. Such screens are powerful for uncovering novel regulators of GO:0071105 and potential therapeutic targets.
Imaging and reporter assays
Live-cell imaging and luciferase reporter assays can monitor IL-11-induced signaling dynamics, including STAT3 nuclear translocation and enhancer activation. These methods provide spatial and temporal resolution of the response to interleukin-11.
How CRISPR Can Be Used to Study GO:0071105 response to interleukin-11
Knockout
CRISPR knockout of IL11, IL11RA or downstream effectors such as STAT3 is used to abolish the response to interleukin-11 and determine its contribution to fibrosis, metastasis and metabolic dysfunction. Knockout cell lines and mice provide definitive loss-of-function models for GO:0071105.
Point Mutation
Point mutations can be introduced into IL11RA or STAT3 to dissect specific residues required for ligand binding, receptor activation or DNA binding. Such models help distinguish between different branches of the IL-11 signaling cascade.
Knock-in
Knock-in of epitope tags or fluorescent reporters into the IL11 or IL11RA loci enables tracking of endogenous protein expression and localization in response to IL-11. This approach is valuable for studying the dynamics of GO:0071105 in vivo.
Overexpression
Overexpression of IL11 or constitutively active STAT3 can mimic chronic IL-11 stimulation and drive pathological phenotypes such as fibrosis and metastasis. These models are useful for testing therapeutic interventions targeting the response to interleukin-11.
How EDITGENE Supports response to interleukin-11 Research
Researchers studying response to interleukin-11-related genes often need to determine whether a candidate gene is causally involved in the pathway or merely correlated with its activation. EDITGENE provides a comprehensive suite of CRISPR-based services to enable such causal studies, from knockout to precise point mutations and overexpression.
Contact EDITGENE today to design your custom CRISPR model for response to interleukin-11 research.
Frequently Asked Questions About response to interleukin-11
What is GO:0071105 response to interleukin-11?
GO:0071105 is a Gene Ontology biological process term defined as any process that results in a change in state or activity of a cell or an organism as a result of an interleukin-11 stimulus.
What genes are involved in response to interleukin-11?
Key genes include IL11, IL11RA, IL6ST (gp130), JAK1/2, STAT3, MAPK1/3, PIK3CA, AKT1, and modulators such as TGFB1 and KRAS.
How does IL-11 signal inside the cell?
IL-11 binds IL11RA, recruits gp130, activates JAK kinases, and phosphorylates STAT3, which then regulates gene expression; MAPK and PI3K/AKT pathways are also engaged.
What diseases are associated with IL-11 signaling?
IL-11 signaling is implicated in cardiovascular fibrosis, cancer metastasis, bone-fat imbalance and metabolic dysfunction.
Is IL-11 a therapeutic target?
Yes, IL-11 is considered a disease gene and therapeutic target, with inhibitors being explored for fibrosis and cancer.
What is the role of IL-11 in bone?
IL-11 mediates a bone-fat linkage in response to mechanical loading, influencing osteoblast and adipocyte differentiation.
How does IL-11 affect metabolism?
IL-11/IL-11RA signaling constrains sphingolipid metabolism to limit the thermogenic capacity of beige adipocytes.
Can CRISPR be used to study IL-11 signaling?
Yes, CRISPR knockout, knock-in, point mutation and overexpression models are widely used to dissect IL-11 pathway causality and identify drug targets.
What is the link between IL-11 and metastasis?
TGF-beta and RAS jointly unmask primed enhancers that cooperate with IL-11 to drive metastatic gene programs.
What experimental models are available for IL-11 research?
Models include IL11 or IL11RA knockout mice, conditional knockouts, CRISPR-engineered cell lines, and overexpression systems for fibrosis, cancer and metabolic studies.
Conclusion
GO:0071105 response to interleukin-11 is a fundamental biological process that orchestrates cellular responses to the cytokine IL-11, with profound implications for fibrosis, cancer, bone metabolism and energy homeostasis. The pathway is complex, involving receptor assembly, JAK/STAT and MAPK activation, transcriptional reprogramming and metabolic outputs. CRISPR-based models are indispensable for establishing causality and developing targeted therapies. As research advances, a deeper understanding of GO:0071105 will likely yield new treatments for fibrotic and metastatic diseases.
References
- 1. Hiasa M et al.. 2024. Bone-fat linkage via interleukin-11 in response to mechanical loading.. J Bone Miner Metab 42(4):447-454 PMID: 38324177
- 2. Cook SA. 2023. Understanding interleukin 11 as a disease gene and therapeutic target.. Biochem J 480(23):1987-2008 PMID: 38054591
- 3. Sweeney M et al.. 2024. Interleukin 11 therapy causes acute left ventricular dysfunction.. Cardiovasc Res 120(17):2220-2235 PMID: 39383190
- 4. Schafer S et al.. 2017. IL-11 is a crucial determinant of cardiovascular fibrosis.. Nature 552(7683):110-115 PMID: 29160304
- 5. Leng SX et al.. 1997. Interleukin-11.. Int J Biochem Cell Biol 29(8-9):1059-62 PMID: 9416001
- 6. Kobayashi S et al.. 1994. Interleukin-11.. Leuk Lymphoma 15(1-2):45-9 PMID: 7532057
- 7. Liu J et al.. 2026. Adipokine IL-11/IL-11Ra constrains sphingolipid metabolism to limit the thermogenic capacity of beige adipocytes.. Cell Metab 38(8):1618-1632.e4 PMID: 42140185
- 8. Lee JH et al.. 2024. TGF-β and RAS jointly unmask primed enhancers to drive metastasis.. Cell 187(22):6182-6199.e29 PMID: 39243762
