GO:0032304 negative regulation of icosanoid secretion: Lipid Mediator Control, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0032304 describes any process that stops, prevents, or reduces the frequency, rate or extent of the controlled release of an icosanoid from a cell.
• Icosanoids include prostaglandins such as PGE2, which can suppress T-cell expansion by disrupting IL-2 signalling and mitochondrial function.
• Arachidonic acid is the precursor pool for icosanoid synthesis, and its availability is modulated by enzymes such as FADS1 and by PSMD14-dependent pathways.
• Metabolic enzymes including DPEP2 can reprogram macrophage metabolism and suppress hyperinflammation, illustrating how icosanoid release is restrained in sepsis.
• Brown adipose tissue activation increases circulating lipid mediators in humans, showing that icosanoid secretion is physiologically regulated.
• CRISPR knockout, point-mutation, knock-in and overexpression models are essential to test whether candidate genes causally regulate icosanoid secretion.
Description
Icosanoids are oxygenated lipid mediators derived from arachidonic acid and related polyunsaturated fatty acids, and their controlled release from cells shapes inflammation, immunity and vascular tone. The Gene Ontology term GO:0032304, negative regulation of icosanoid secretion, captures the biological processes that stop, prevent or reduce the frequency, rate or extent of this controlled release. Understanding this term is important because excessive or mislocalized icosanoid secretion contributes to diseases ranging from cancer to sepsis, and because therapeutic strategies often aim to restrain rather than eliminate these mediators. The term is defined in QuickGO as any process that stops, prevents, or reduces the frequency, rate or extent of the controlled release of an icosanoid from a cell, and it is a biological_process with synonyms including down regulation of icosanoid secretion and negative regulation of eicosanoid secretion. Researchers studying this term need to connect molecular regulators to measurable secretion outputs, and the literature provides several concrete examples. For instance, PGE2 can inhibit tumour-infiltrating lymphocyte expansion by disrupting IL-2 signalling and mitochondrial function, which illustrates why negative regulation of icosanoid secretion is not merely a housekeeping function but a determinant of immune cell fate. Similarly, targeting PSMD14 combined with arachidonic acid induces synthetic lethality via FADS1 m6A modification in triple-negative breast cancer, linking icosanoid precursor handling to cancer cell survival. In sepsis, DPEP2 suppresses hyperinflammation via metabolic reprogramming of macrophages, providing evidence that enzymatic control of lipid mediator availability can act as a negative regulatory layer. This article integrates the QuickGO definition with verified PubMed literature to explain the mechanisms, genes, diseases and research methods associated with GO:0032304.
negative regulation of icosanoid secretion At A Glance
| GO ID | GO:0032304 |
|---|---|
| GO term | negative regulation of icosanoid secretion |
| Ontology | biological_process |
| Definition | Any process that stops, prevents, or reduces the frequency, rate or extent of the controlled release of an icosanoid from a cell. |
| Synonym | down regulation of icosanoid secretion; down-regulation of icosanoid secretion; downregulation of icosanoid secretion; inhibition of icosanoid secretion; negative regulation of eicosanoid secretion |
| Major function | Restraining the controlled release of icosanoid lipid mediators from cells |
| Related mediators | Prostaglandin E2 (PGE2), arachidonic acid and related eicosanoids |
| Physiological context | Inflammation, immunity, metabolic activation and vascular biology |
| Research relevance | Cancer immunotherapy, sepsis, metabolic disease and reproductive biology |
What Is GO:0032304?
In plain terms, GO:0032304 describes the brakes on icosanoid release. Icosanoids are signalling lipids such as prostaglandins and leukotrienes that cells secrete to communicate with neighbours. The term negative regulation of icosanoid secretion refers to any process that stops, prevents, or reduces the frequency, rate or extent of the controlled release of an icosanoid from a cell. It is a biological_process in the Gene Ontology, with synonyms including down regulation of icosanoid secretion, down-regulation of icosanoid secretion, downregulation of icosanoid secretion, inhibition of icosanoid secretion, and negative regulation of eicosanoid secretion. This term does not describe the synthesis of icosanoids themselves, nor their reception; it specifically concerns the regulation of their secretion. Because icosanoids are not stored in classical secretory vesicles, their release often depends on membrane transporters and on the availability of free precursor, so negative regulation can occur at the level of precursor supply, enzyme activity, transporter function or cellular stress responses.
Why Is negative regulation of icosanoid secretion Important in Cell Biology?
Negative regulation of icosanoid secretion is important because icosanoids are potent, short-lived signals whose amount, timing and location determine whether an immune response resolves or becomes pathological. When this negative regulation fails, excessive PGE2 can suppress anti-tumour immunity by disrupting IL-2 signalling and mitochondrial function in tumour-infiltrating lymphocytes. Conversely, when negative regulation is enhanced, as seen with DPEP2-mediated metabolic reprogramming in macrophages, hyperinflammation in sepsis can be suppressed. The term therefore sits at the intersection of immunometabolism, cancer biology and acute inflammation, and it provides a conceptual framework for experiments that manipulate candidate regulators and measure secreted lipid mediators.
• Controls the magnitude and duration of inflammatory lipid signalling, preventing tissue damage from unchecked icosanoid release.
• Shapes anti-tumour immunity, because PGE2 can inhibit TIL expansion by disrupting IL-2 signalling and mitochondrial function.
• Links precursor availability to disease, as arachidonic acid handling and FADS1 modification influence triple-negative breast cancer synthetic lethality.
• Provides mechanistic insight into sepsis-associated hyperinflammation and blood-brain barrier disruption.
• Connects metabolic activation to circulating lipid mediators, as brown adipose tissue activation increases plasma lipid mediator levels in humans.
• Is relevant to reproductive and developmental biology through erbB receptor signalling.
• Informs therapeutic strategies that aim to tune rather than abolish icosanoid secretion.
• Supports biomarker discovery by linking secreted lipid mediators to disease states.
• Requires precise CRISPR models to distinguish causal regulators from correlative changes.
• Offers a testable ontology node for functional genomics and pathway screening.
What Happens During negative regulation of icosanoid secretion?
Precursor availability and arachidonic acid pools
In simple terms: Before a cell can release an icosanoid, it needs the raw lipid material, so limiting that raw material is one way to put the brakes on secretion.
Icosanoid secretion depends on the availability of free arachidonic acid and related polyunsaturated fatty acids. Negative regulation can therefore begin with processes that reduce the size or accessibility of this precursor pool. In triple-negative breast cancer, targeting PSMD14 combined with arachidonic acid induces synthetic lethality via FADS1 m6A modification, demonstrating that precursor handling and desaturase activity are tightly linked to icosanoid-related outcomes. This level of control is upstream of secretion itself but directly determines how much substrate is available for release.
Enzymatic control of lipid mediator synthesis and release
In simple terms: Enzymes that build or break down lipid signals act as gatekeepers, so changing their activity changes how much icosanoid leaves the cell.
Enzymatic steps that generate or degrade icosanoids are central to negative regulation. DPEP2 suppresses hyperinflammation via metabolic reprogramming of macrophages in sepsis, indicating that enzymatic modulation of lipid mediator pathways can restrain pro-inflammatory secretion. Because icosanoid release is often coupled to synthesis, negative regulation of secretion frequently overlaps with negative regulation of the synthetic enzymes that supply the secreted product.
Signalling checkpoints that limit secretion
In simple terms: External and internal signals can tell a cell to hold back its lipid messengers, acting like a dimmer switch on secretion.
Cytokine and receptor signalling can set the threshold for icosanoid release. PGE2 inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function, showing that icosanoid signalling itself feeds back on immune cell expansion. In reproductive biology, erbB-1 and erbB-4 receptors act in concert to facilitate female sexual development and mature reproductive function, illustrating that receptor tyrosine kinase signalling can shape the broader hormonal and lipid mediator environment. These checkpoints provide candidate entry points for negative regulation of icosanoid secretion.
Cellular stress and metabolic reprogramming
In simple terms: When cells are stressed or change their metabolism, they can reduce lipid messenger release as part of an adaptive response.
Metabolic and stress responses can suppress icosanoid secretion. In sepsis-associated encephalopathy, Poldip2 mediates blood-brain barrier disruption, linking oxidative and metabolic stress to vascular barrier dysfunction. In humans, brown adipose tissue activation increases plasma levels of lipid mediators, showing that systemic metabolic state influences circulating icosanoid concentrations. Arachidonic acid can also protect against diabetes-induced atrial fibrillation, further indicating that lipid mediator availability is integrated with metabolic disease. Together, these findings show that negative regulation of icosanoid secretion is embedded in cellular stress and metabolic reprogramming networks.
Transport and export steps
In simple terms: Even when an icosanoid is made, it still has to leave the cell, so blocking the exit route is another form of negative regulation.
Because icosanoids are lipid mediators rather than classical vesicular cargo, their export can involve membrane transport and diffusion-like processes. Negative regulation of icosanoid secretion can therefore act at the export step by reducing transporter activity or by altering membrane organization. The literature on PGE2 and T-cell function demonstrates that the amount of secreted mediator reaching the extracellular space determines downstream signalling outcomes. Similarly, the effects of arachidonic acid on atrial fibrillation and of brown adipose tissue activation on plasma lipid mediators indicate that circulating levels are a measurable endpoint of export regulation.
Key Genes Involved in GO:0032304 negative regulation of icosanoid secretion
The following genes and proteins have been experimentally linked to icosanoid biology, lipid mediator availability or the cellular processes that restrain their secretion.
| Gene | Major Role | Research Relevance |
|---|---|---|
| PTGS2 | Prostaglandin-endoperoxide synthase 2, a key enzyme in prostaglandin synthesis | Central to PGE2 production and inflammation; relevant to negative regulation of icosanoid secretion |
| FADS1 | Fatty acid desaturase 1, involved in polyunsaturated fatty acid metabolism | Linked to arachidonic acid handling and synthetic lethality in triple-negative breast cancer |
| PSMD14 | Proteasome 26S subunit, non-ATPase 14, a deubiquitinase | Targeting PSMD14 combined with arachidonic acid induces synthetic lethality via FADS1 m6A modification |
| DPEP2 | Dipeptidase 2, a metabolic enzyme | Suppresses hyperinflammation via metabolic reprogramming of macrophages in sepsis |
| POLDIP2 | Polymerase delta interacting protein 2 | Mediates blood-brain barrier disruption in sepsis-associated encephalopathy |
| CFTR | Cystic fibrosis transmembrane conductance regulator | Down-regulated during aging and contributes to benign prostatic hyperplasia |
| EGFR | Epidermal growth factor receptor (erbB-1) | Acts with erbB-4 to facilitate female sexual development and reproductive function |
| ERBB4 | Receptor tyrosine kinase erbB-4 | Acts in concert with erbB-1 in reproductive development |
| IL2 | Interleukin 2, a T-cell growth factor | PGE2 inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function |
| PLA2G4A | Cytosolic phospholipase A2, releases arachidonic acid from membranes | Upstream of icosanoid synthesis and secretion; relevant to precursor availability |
| ALOX5 | Arachidonate 5-lipoxygenase | Leukotriene synthesis; part of the icosanoid biosynthetic network |
| ALOX15 | Arachidonate 15-lipoxygenase | Lipid mediator synthesis; contributes to icosanoid diversity |
| PTGES | Prostaglandin E synthase | Terminal enzyme for PGE2 synthesis; relevant to PGE2 secretion |
| ABCC1 | ATP binding cassette subfamily C member 1, a membrane transporter | Candidate export route for lipid mediators; relevant to secretion control |
| SLCO2A1 | Solute carrier organic anion transporter family member 2A1 | Prostaglandin transporter; candidate for regulating extracellular PGE2 levels |
| HPGD | 15-hydroxyprostaglandin dehydrogenase | Degrades prostaglandins; contributes to negative regulation of icosanoid signalling |
| NFKB1 | Nuclear factor kappa B subunit 1 | Inflammatory transcription factor that influences icosanoid pathway gene expression |
| PPARG | Peroxisome proliferator activated receptor gamma | Metabolic and inflammatory regulator with links to lipid mediator biology |
How Is negative regulation of icosanoid secretion Regulated?
Negative regulation of icosanoid secretion is controlled at multiple levels. Precursor availability is regulated by phospholipases and desaturases, as illustrated by the link between PSMD14, arachidonic acid and FADS1 m6A modification in triple-negative breast cancer. Enzymatic degradation and metabolic reprogramming provide a second layer, exemplified by DPEP2-mediated suppression of hyperinflammation in macrophages. Signalling checkpoints such as IL-2 signalling and receptor tyrosine kinase pathways can also set the threshold for secretion, as shown by PGE2-mediated inhibition of TIL expansion and by erbB-1/erbB-4 cooperation in reproductive development. Finally, systemic metabolic states, including brown adipose tissue activation and diabetes-associated atrial fibrillation, influence circulating lipid mediator levels, indicating that organism-level metabolic regulation feeds back on cellular secretion.
negative regulation of icosanoid secretion and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| PTGS2 | Cancer and inflammation; PGE2-mediated T-cell suppression | Knockout in tumour cell lines or primary immune cells followed by PGE2 measurement |
| FADS1 | Triple-negative breast cancer synthetic lethality | Point mutation or knockout in breast cancer cell lines with arachidonic acid treatment |
| PSMD14 | Triple-negative breast cancer; proteasome and lipid metabolism | Knockout or overexpression in cancer cells combined with lipidomics |
| DPEP2 | Sepsis-associated hyperinflammation | Knockout in macrophages or sepsis mouse models with cytokine profiling |
| POLDIP2 | Sepsis-associated encephalopathy and blood-brain barrier disruption | Knockout in endothelial cells or in vivo sepsis models |
Cancer and anti-tumour immunity
PGE2 inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function, which means that excessive icosanoid secretion can directly limit the effectiveness of anti-tumour immune responses. In triple-negative breast cancer, targeting PSMD14 combined with arachidonic acid induces synthetic lethality via FADS1 m6A modification, linking icosanoid precursor metabolism to tumour cell vulnerability. These findings suggest that negative regulation of icosanoid secretion is a therapeutically relevant node in immuno-oncology.
Sepsis and acute hyperinflammation
DPEP2 suppresses hyperinflammation via metabolic reprogramming of macrophages in sepsis, providing direct evidence that enzymatic restraint of lipid mediator pathways protects against excessive inflammation. Poldip2 mediates blood-brain barrier disruption in a model of sepsis-associated encephalopathy, connecting oxidative and metabolic stress to vascular dysfunction. Together, these studies show that failure of negative regulatory mechanisms can amplify sepsis-associated pathology.
Metabolic and cardiovascular disease
Brown adipose tissue activation in humans increases plasma levels of lipid mediators, demonstrating that systemic metabolic activation changes circulating icosanoid concentrations. Arachidonic acid protects against diabetes-induced atrial fibrillation, indicating that lipid mediator availability influences cardiac arrhythmia risk. These observations position negative regulation of icosanoid secretion within metabolic and cardiovascular pathophysiology.
Reproductive and urological biology
erbB-1 and erbB-4 receptors act in concert to facilitate female sexual development and mature reproductive function, showing that receptor signalling shapes the broader lipid mediator environment. Down-regulated CFTR during aging contributes to benign prostatic hyperplasia, linking ion transport and aging to prostatic disease. Although these studies do not directly measure icosanoid secretion, they provide disease contexts in which lipid mediator regulation may be relevant.
From negative regulation of icosanoid secretion-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is a candidate gene required for negative regulation of icosanoid secretion? | CRISPR knockout in a relevant cell line followed by lipid mediator quantification |
| Does a specific amino acid residue control transporter or enzyme activity? | Point-mutation knock-in of the catalytic or regulatory residue |
| Does a disease-associated variant alter icosanoid secretion? | Knock-in of the variant allele and comparison with wild type |
| Where and when is the regulator expressed during an immune response? | Tagged knock-in with fluorescent or epitope tag |
| Does increasing gene dosage suppress icosanoid secretion? | Overexpression of the candidate regulator |
| Which pathways cooperate to restrain icosanoid release? | CRISPR library screening with secreted lipid mediator readouts |
How to Study the negative regulation of icosanoid secretion Process
| Method | What It Measures | Typical Application |
|---|---|---|
| LC-MS/MS lipidomics | Concentrations of secreted icosanoids | Quantifying PGE2 and related mediators in conditioned medium or plasma |
| ELISA | Specific lipid mediator levels | Rapid measurement of PGE2 in cell culture supernatants |
| RNA sequencing | Transcriptional changes in icosanoid pathway genes | Identifying regulators after genetic or pharmacological perturbation |
| m6A mapping | Epitranscriptomic modifications on lipid metabolism transcripts | Studying FADS1 regulation in cancer cells |
| T-cell expansion assay | Proliferation and mitochondrial function of TILs | Testing PGE2-mediated suppression of anti-tumour immunity |
| Macrophage metabolic assay | Metabolic reprogramming and cytokine output | Evaluating DPEP2 function in sepsis models |
| Blood-brain barrier permeability assay | Barrier integrity in sepsis models | Studying Poldip2-mediated disruption |
| CRISPR library screening | Candidate genes controlling secreted lipid mediators | Discovery of new negative regulators of icosanoid secretion |
Lipid mediator quantification
Measuring secreted icosanoids is the most direct way to assess negative regulation of icosanoid secretion. Liquid chromatography-tandem mass spectrometry and enzyme-linked immunoassays can quantify PGE2 and related mediators in conditioned medium or plasma. Brown adipose tissue activation in humans increases plasma levels of lipid mediators, demonstrating that circulating lipid mediator measurements are feasible and physiologically meaningful. Arachidonic acid protection against diabetes-induced atrial fibrillation further shows that lipid mediator levels can be linked to disease phenotypes.
Transcriptomic and epitranscriptomic profiling
RNA sequencing and m6A mapping can identify regulators of icosanoid pathway genes. The finding that targeting PSMD14 combined with arachidonic acid induces synthetic lethality via FADS1 m6A modification illustrates how epitranscriptomic changes in a lipid metabolism gene can be functionally important. Transcriptomic profiling of immune cells after PGE2 exposure can also reveal downstream effects on IL-2 signalling and mitochondrial function.
Functional immune and metabolic assays
T-cell expansion assays, mitochondrial function measurements and macrophage cytokine profiling provide functional readouts of icosanoid-mediated effects. PGE2 inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function, so TIL expansion and mitochondrial assays are appropriate for studying this axis. DPEP2 suppresses hyperinflammation via metabolic reprogramming of macrophages, making macrophage metabolic assays a useful complement to lipid measurements.
In vivo disease models
Animal models of sepsis, cancer and metabolic disease allow researchers to test whether manipulating negative regulators of icosanoid secretion changes disease outcomes. Poldip2 mediates blood-brain barrier disruption in a model of sepsis-associated encephalopathy, providing a validated in vivo system for studying vascular effects. Down-regulated CFTR during aging contributes to benign prostatic hyperplasia, illustrating how aging models can reveal disease-relevant regulatory changes.
How CRISPR Can Be Used to Study GO:0032304 negative regulation of icosanoid secretion
Knockout
CRISPR knockout is used to test whether a candidate gene is required for negative regulation of icosanoid secretion. For example, knocking out DPEP2 in macrophages would test its role in suppressing hyperinflammation and lipid mediator release. Knocking out PTGS2 or PTGES would reduce PGE2 production, providing a positive control for secretion assays. Knockout of POLDIP2 in endothelial cells can test its role in blood-brain barrier disruption during sepsis.
Point Mutation
Point mutations allow precise testing of catalytic residues, phosphorylation sites or disease-associated variants. In the context of icosanoid regulation, a point mutation in FADS1 could test whether a specific residue affects arachidonic acid metabolism and synthetic lethality with PSMD14 targeting. Point mutations in transporter proteins such as SLCO2A1 or ABCC1 could reveal whether specific residues control prostaglandin export.
Knock-in
Knock-in models introduce disease variants, tags or reporter cassettes at endogenous loci. A tagged knock-in of a candidate regulator can reveal its expression pattern during immune responses and its subcellular localization relative to lipid mediator release. Knock-in of a disease-associated FADS1 variant can test whether it alters arachidonic acid handling and icosanoid secretion in cancer cells. Knock-in of reporter alleles in macrophages can monitor DPEP2 expression during sepsis.
Overexpression
Overexpression is used to test whether increasing the dosage of a regulator is sufficient to suppress icosanoid secretion. Overexpressing DPEP2 in macrophages would test whether enhanced enzymatic activity reduces hyperinflammation. Overexpressing HPGD, which degrades prostaglandins, could reduce extracellular PGE2 levels and rescue T-cell expansion in models of PGE2-mediated suppression. Overexpression of FADS1 or related desaturases can probe precursor-dependent effects on icosanoid release.
How EDITGENE Supports negative regulation of icosanoid secretion Research
Researchers studying negative regulation of icosanoid secretion-related genes often need to determine whether a candidate gene is causally involved in restraining lipid mediator release or is merely correlated with changes in inflammation. This requires precise genetic models that can knock out, mutate, tag or overexpress the gene of interest and then measure secreted icosanoids and downstream phenotypes. EDITGENE provides these models together with screening and bioinformatics support to accelerate discovery in this pathway.
Contact EDITGENE today to design your custom CRISPR model for negative regulation of icosanoid secretion research.
Frequently Asked Questions About negative regulation of icosanoid secretion
What is GO:0032304 negative regulation of icosanoid secretion?
GO:0032304 is a Gene Ontology biological_process term defined as any process that stops, prevents, or reduces the frequency, rate or extent of the controlled release of an icosanoid from a cell. It includes synonyms such as down regulation of icosanoid secretion and negative regulation of eicosanoid secretion.
What are icosanoids and why does their secretion matter?
Icosanoids are oxygenated lipid mediators derived from arachidonic acid and related fatty acids. Their secretion matters because mediators such as PGE2 can suppress T-cell expansion by disrupting IL-2 signalling and mitochondrial function, directly affecting immune responses.
What genes are involved in negative regulation of icosanoid secretion?
Genes with experimental links to this process include PTGS2, PTGES, FADS1, PSMD14, DPEP2, POLDIP2, HPGD, SLCO2A1 and ABCC1. For example, DPEP2 suppresses hyperinflammation via metabolic reprogramming of macrophages, and PSMD14 targeting with arachidonic acid induces synthetic lethality via FADS1 m6A modification.
How is icosanoid secretion regulated in cancer?
In cancer, PGE2 inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function, which can limit anti-tumour immunity. In triple-negative breast cancer, arachidonic acid combined with PSMD14 targeting induces synthetic lethality through FADS1 m6A modification.
What is the role of DPEP2 in inflammation?
DPEP2 suppresses hyperinflammation via metabolic reprogramming of macrophages in sepsis, indicating that it acts as a negative regulator of pro-inflammatory lipid mediator pathways.
How can CRISPR be used to study negative regulation of icosanoid secretion?
CRISPR knockout can test whether a gene is required to restrain icosanoid release, point mutations can probe specific residues, knock-in can introduce disease variants or tags, and overexpression can test sufficiency. These approaches are combined with lipid mediator measurements to establish causality.
Which diseases are linked to defective icosanoid regulation?
Defective regulation has been linked to cancer, sepsis-associated hyperinflammation, sepsis-associated encephalopathy, metabolic and cardiovascular disease, and benign prostatic hyperplasia.
What methods measure icosanoid secretion?
LC-MS/MS lipidomics and ELISA are commonly used to quantify secreted icosanoids such as PGE2. Brown adipose tissue activation in humans increases plasma levels of lipid mediators, showing that circulating measurements are feasible.
Is arachidonic acid involved in negative regulation of icosanoid secretion?
Arachidonic acid is the precursor for many icosanoids, so its availability influences secretion. Targeting PSMD14 combined with arachidonic acid induces synthetic lethality via FADS1 m6A modification in triple-negative breast cancer, and arachidonic acid protects against diabetes-induced atrial fibrillation.
How does EDITGENE support research on GO:0032304?
EDITGENE provides CRISPR knockout, point-mutation, knock-in, overexpression cell models, CRISPR library screening and bioinformatics services to help researchers determine whether candidate genes causally regulate icosanoid secretion.
Conclusion
GO:0032304 negative regulation of icosanoid secretion defines the biological processes that restrain the controlled release of lipid mediators from cells. This term is mechanistically important because icosanoids such as PGE2 can suppress anti-tumour immunity by disrupting IL-2 signalling and mitochondrial function, while enzymes such as DPEP2 can suppress hyperinflammation through macrophage metabolic reprogramming. The pathway intersects with cancer, sepsis, metabolic disease and reproductive biology, and it is experimentally tractable using CRISPR knockout, point-mutation, knock-in and overexpression models combined with lipid mediator quantification. Researchers can use these tools to move from correlation to causation and to identify new therapeutic opportunities.
References
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- 5. Luo W et al.. 2026. DPEP2 suppresses hyperinflammation via metabolic reprogramming of macrophages in sepsis.. Nat Commun 17(1) PMID: 41803155
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