GO:0032711 negative regulation of interleukin-27 production: Immune Checkpoint Control, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0032711 describes any process that stops, prevents, or reduces the frequency, rate, or extent of interleukin-27 (IL-27) production, a key cytokine checkpoint in innate and adaptive immunity.
• IL-27 is a heterodimeric cytokine of the IL-12 family, and its production is tightly controlled at transcriptional and post-transcriptional levels in monocytes, neutrophils, and dendritic cells.
• Negative regulation of IL-27 production is critical for limiting excessive inflammation, but dysregulation is linked to bacterial sepsis, allergic rhinitis, and tuberculous pleural effusion.
• Human neutrophils and monocytes are major sources of IL-27, and autocrine/paracrine feedback loops suppress its production during bacterial infection.
• Experimental models for studying GO:0032711 include CRISPR knockout of IL27 subunits (IL27, EBI3), point mutations in regulatory elements, and overexpression of negative regulators.
• EDITGENE provides CRISPR knockout, point mutation, knock-in, overexpression cell models, and library screening to dissect the genetic control of IL-27 production.
Description
Interleukin-27 (IL-27) is a pleiotropic cytokine of the IL-12 family that regulates innate and adaptive immune responses. Its production must be tightly controlled because excessive IL-27 can suppress protective immunity, while insufficient IL-27 contributes to uncontrolled inflammation. GO:0032711, negative regulation of interleukin-27 production, captures the biological processes that restrain IL-27 synthesis at the transcriptional, post-transcriptional, and secretory levels. Understanding this term is essential for immunologists studying host-pathogen interactions, autoimmunity, and cytokine networks. Recent studies have shown that human neutrophils and monocytes produce IL-27 during bacterial infection, and that IL-27 in turn regulates their function through feedback inhibition. Negative regulation of IL-27 production therefore acts as an immune checkpoint that prevents cytokine-driven pathology. In neonatal sepsis models, inhibition of IL-27 signaling improves disease outcomes by modulating chemokine levels and sustaining CXCR2 expression on mononuclear cells. These findings highlight the therapeutic potential of targeting pathways that control IL-27 production. For researchers, GO:0032711 provides a framework to identify genes and signaling cascades that suppress IL-27. Key negative regulators include IL-10, TGF-beta, and SOCS proteins, although the exact mechanisms remain an active area of investigation. This article synthesizes current knowledge from QuickGO and PubMed to guide experimental design using CRISPR-based models.
negative regulation of interleukin-27 production At A Glance
| GO ID | GO:0032711 |
|---|---|
| GO term | negative regulation of interleukin-27 production |
| Ontology | biological_process |
| Synonym | negative regulation of IL-27 production; inhibition of interleukin-27 production; downregulation of interleukin-27 production |
| Major function | Suppression of IL-27 cytokine biosynthesis and release, limiting its immunomodulatory effects |
| Cellular context | Monocytes, neutrophils, dendritic cells, and other innate immune cells |
| Upstream regulators | IL-10, TGF-beta, SOCS proteins, and pathogen-derived signals |
| Disease relevance | Bacterial sepsis, allergic rhinitis, tuberculous pleural effusion |
| Research methods | CRISPR knockout, RNA-seq, cytokine profiling, flow cytometry |
What Is GO:0032711?
GO:0032711, negative regulation of interleukin-27 production, is defined by QuickGO as any process that stops, prevents, or reduces the frequency, rate, or extent of interleukin-27 production. This includes inhibition of IL-27 biosynthesis, secretion, or release from cells such as monocytes, neutrophils, and dendritic cells. The term encompasses both cell-intrinsic mechanisms (e.g., transcriptional repression) and extracellular signals (e.g., cytokines) that downregulate IL-27 levels.
Why Is negative regulation of interleukin-27 production Important in Cell Biology?
Negative regulation of IL-27 production is critical for balancing protective immunity and immunopathology. IL-27 can suppress T helper 17 (Th17) responses and limit excessive inflammation, but uncontrolled IL-27 production may impair pathogen clearance. In bacterial sepsis, IL-27 contributes to immune suppression, and its negative regulation is associated with improved outcomes. Understanding GO:0032711 helps researchers identify therapeutic targets to modulate IL-27 levels in infectious and inflammatory diseases.
• Controls the magnitude and duration of IL-27-driven immune responses during bacterial infection.
• Prevents excessive IL-27-mediated suppression of neutrophil and monocyte function.
• Modulates Th17 inflammation in allergic diseases such as allergic rhinitis.
• Influences disease outcomes in neonatal gram-negative sepsis by regulating chemokine levels and CXCR2 expression.
• Provides a checkpoint for cytokine networks in tuberculous pleural effusion.
• Offers a target for host-directed therapies in sepsis and inflammatory disorders.
• Helps explain inter-individual variability in IL-27 levels and immune responses.
• Guides CRISPR-based screens to discover novel negative regulators of IL-27.
• Supports biomarker development for IL-27-associated diseases.
• Enables mechanistic studies of cytokine crosstalk in innate immunity.
What Happens During negative regulation of interleukin-27 production?
Initiation by extracellular signals
In simple terms: External signals tell immune cells to stop making IL-27.
Negative regulation of IL-27 production is often initiated by anti-inflammatory cytokines such as IL-10 and TGF-beta, which are released during the resolution phase of inflammation. Pathogen-derived molecules can also trigger feedback inhibition of IL-27 in neutrophils and monocytes. These signals activate intracellular cascades that converge on the IL27 and EBI3 gene promoters.
Transcriptional repression of IL27 and EBI3
In simple terms: The genes that make IL-27 are switched off.
IL-27 is a heterodimer of IL-27p28 (encoded by IL27) and EBI3. Negative regulation involves reduced transcription of both subunits, mediated by transcription factors such as STAT3 and SOCS proteins. In human monocytes, IL-27 acts as an endogenous constitutive repressor, suggesting autocrine feedback that limits its own production.
Post-transcriptional and secretory control
In simple terms: Even if the genes are on, the protein can be blocked from being released.
Beyond transcription, negative regulation can occur through mRNA destabilization, inhibition of translation, or blockade of secretion. In neutrophils, IL-27 production is rapidly downregulated after bacterial challenge, consistent with post-transcriptional control. The exact molecular players remain to be fully defined but likely include RNA-binding proteins and microRNAs.
Feedback loops and cellular crosstalk
In simple terms: IL-27 itself can turn down its own production.
IL-27 can suppress its own production in an autocrine manner, as shown in human monocytes where IL-27 acts as a constitutive repressor. This feedback loop prevents sustained IL-27 signaling that could otherwise impair antimicrobial immunity. In neonatal sepsis, inhibition of IL-27 signaling alters chemokine profiles and sustains CXCR2 expression, indicating that negative regulation of IL-27 production is part of a broader cytokine network.
Integration with metabolic and inflammatory pathways
In simple terms: Metabolism and inflammation influence how much IL-27 is made.
IL-27 influences metabolic fitness in murine neonatal sepsis, and metabolic cues may reciprocally regulate IL-27 production. Inflammatory mediators such as TNF-alpha and IL-1beta can either enhance or suppress IL-27 depending on context. This integration ensures that IL-27 levels are tailored to the immune-metabolic state of the host.
Key Genes Involved in GO:0032711 negative regulation of interleukin-27 production
The following genes and proteins are central to the negative regulation of interleukin-27 production, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| IL27 | Encodes IL-27p28 subunit; its transcription is a target of negative regulation | CRISPR knockout to abolish IL-27 production; promoter studies |
| EBI3 | Encodes EBI3 subunit of IL-27; co-regulated with IL27 | Knockout models to study heterodimer assembly |
| IL10 | Anti-inflammatory cytokine that suppresses IL-27 production | Overexpression or knockout to test upstream regulation |
| TGFB1 | Inhibits IL-27 production in monocytes and dendritic cells | Point mutations in signaling domains |
| SOCS1 | Suppressor of cytokine signaling; inhibits IL-27-induced pathways | Knockout to enhance IL-27 responses |
| SOCS3 | Negative regulator of cytokine signaling; may suppress IL-27 production | CRISPR knockout in immune cells |
| STAT3 | Transcription factor mediating IL-10 and IL-27 feedback | Knock-in of phospho-mutants |
| STAT1 | Mediates IFN-gamma effects on IL-27 | Knockout to assess IFN-IL-27 axis |
| NFKB1 | Inflammatory transcription factor that can modulate IL-27 | Overexpression and reporter assays |
| IRF1 | Interferon regulatory factor involved in IL-27 induction | Knockout to study IFN-driven IL-27 |
| CXCR2 | Chemokine receptor whose expression is sustained when IL-27 signaling is inhibited | Knockout in mononuclear cells |
| IL27RA | IL-27 receptor subunit; mediates feedback on IL-27 production | Knockout to block autocrine feedback |
| IL6ST | gp130 subunit shared by IL-27 receptor; links to STAT signaling | Point mutations in signaling domains |
| TNF | Pro-inflammatory cytokine that can influence IL-27 levels | Overexpression or neutralization |
| IL1B | Inflammatory cytokine modulating IL-27 in infection | Knockout in macrophages |
| TLR4 | Pattern recognition receptor triggering IL-27 responses to LPS | Knockout in neutrophils |
| MYD88 | Adaptor downstream of TLRs; affects IL-27 production | Knockout to test TLR-dependent regulation |
| FOXP3 | Regulatory T cell marker linked to IL-27-mediated suppression | Overexpression in T cells |
How Is negative regulation of interleukin-27 production Regulated?
Negative regulation of IL-27 production is controlled by a network of cytokines, transcription factors, and signaling pathways. IL-10 and TGF-beta are potent suppressors of IL-27 in monocytes and dendritic cells. SOCS proteins, induced by cytokines, inhibit JAK-STAT signaling and reduce IL-27 transcription. Autocrine IL-27 signaling through IL27RA and gp130 can feedback to limit its own production. In neonatal sepsis, inhibition of IL-27 signaling modulates chemokine levels and sustains CXCR2 expression, indicating that inflammatory mediators reciprocally regulate IL-27. Metabolic pathways may also influence IL-27 production, as IL-27 affects metabolic fitness in murine sepsis models.
negative regulation of interleukin-27 production and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| IL27 | Neonatal sepsis; bacterial infection | IL27 knockout mice; CRISPR knockout in human monocytes |
| EBI3 | Allergic rhinitis; Th17 inflammation | EBI3 knockout mice; overexpression in T cells |
| IL27RA | Tuberculous pleural effusion | IL27RA knockout mice; knock-in of signaling mutants |
| CXCR2 | Gram-negative neonatal sepsis | CXCR2 knockout mononuclear cells; CRISPR point mutation |
| SOCS1 | Cytokine signaling dysregulation | SOCS1 knockout macrophages; overexpression |
Bacterial sepsis and neonatal infection
IL-27 is a key regulator of innate immunity during bacterial infection, and its negative regulation is critical for controlling microbial growth. In neonatal gram-negative sepsis, inhibition of IL-27 signaling improves disease outcomes by regulating chemokine levels and sustaining CXCR2 on mononuclear cells. IL-27 also influences metabolic fitness in murine neonatal sepsis, linking immune regulation to metabolism. These findings suggest that targeting pathways that negatively regulate IL-27 production could be therapeutically beneficial.
Allergic rhinitis and Th17 inflammation
IL-27 suppresses T helper 17 (Th17) inflammation in allergic rhinitis, and negative regulation of IL-27 production may exacerbate Th17-driven pathology. Understanding how IL-27 production is downregulated could inform therapies for allergic diseases.
Tuberculous pleural effusion
Exogenous intrapleural injection of IL-27 may improve outcomes in patients with tuberculous pleural effusion, suggesting that endogenous negative regulation of IL-27 production could limit protective immunity. Modulating IL-27 levels may therefore have prognostic and therapeutic implications.
Neutrophil and monocyte dysfunction
IL-27 acts as a negative regulator of human neutrophil function, and its production by neutrophils is downregulated during bacterial infection. Dysregulated negative regulation of IL-27 production could impair neutrophil antimicrobial activity. Monocytes also produce IL-27, and its autocrine repression influences their function.
From negative regulation of interleukin-27 production-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X negatively regulate IL-27 production? | CRISPR knockout of gene X in human monocytes or neutrophils, followed by IL-27 ELISA |
| Which regulatory elements control IL27 transcription? | Point mutations in IL27 promoter via CRISPR base editing |
| Does a disease-associated SNP affect IL-27 levels? | Knock-in of the SNP in immortalized immune cells |
| Can overexpression of a negative regulator suppress IL-27? | Lentiviral overexpression of candidate gene in macrophages |
| What is the role of IL-27 feedback in sepsis? | IL27RA knockout mice in neonatal sepsis model |
| How does IL-27 production change during bacterial infection? | CRISPR knockout of TLR4 or MYD88 in neutrophils |
How to Study the negative regulation of interleukin-27 production Process
| Method | What It Measures | Typical Application |
|---|---|---|
| ELISA | IL-27 protein concentration | Quantify negative regulation in knockout cells |
| RNA-seq | Transcript levels of IL27, EBI3, and regulators | Identify transcriptional networks |
| Flow cytometry | Intracellular IL-27 and surface CXCR2 | Analyze cell-specific production |
| CRISPR knockout screen | Genes whose loss alters IL-27 production | Discover novel negative regulators |
| Western blot | Protein levels of signaling intermediates | Validate SOCS/STAT pathways |
| Reporter assay | IL27 promoter activity | Test regulatory elements |
| Proteomics | Global protein changes | Uncover post-transcriptional regulation |
| Bioinformatics pathway analysis | Enriched pathways in screen hits | Interpret CRISPR screen data |
Cytokine profiling by ELISA and Luminex
Quantification of IL-27 protein levels in culture supernatants or serum is the primary method to assess negative regulation of IL-27 production. ELISA and multiplex assays allow comparison between wild-type and CRISPR-edited cells.
RNA-seq and transcriptomics
RNA sequencing can identify transcriptional changes in IL27 and EBI3, as well as global pathways that negatively regulate IL-27. This approach is useful for discovering novel regulators in knockout models.
Flow cytometry and intracellular staining
Flow cytometry enables detection of IL-27-producing cells and assessment of surface markers such as CXCR2 in mononuclear cells. Intracellular cytokine staining can identify which cell types downregulate IL-27.
CRISPR screens and functional genomics
Genome-wide CRISPR knockout screens can uncover genes whose loss increases IL-27 production, thereby identifying negative regulators. These screens are complemented by bioinformatics analysis of pathways enriched in hits.
How CRISPR Can Be Used to Study GO:0032711 negative regulation of interleukin-27 production
Knockout
CRISPR knockout of candidate negative regulators (e.g., IL10, SOCS1, IL27RA) in human monocytes or neutrophils can test whether their loss increases IL-27 production. Knockout of IL27 or EBI3 abolishes IL-27 production and serves as a positive control.
Point Mutation
Point mutations in IL27 promoter or signaling domains of STAT3 can dissect specific regulatory elements controlling IL-27 production. Base editing allows introduction of disease-associated SNPs to study their impact on IL-27 levels.
Knock-in
Knock-in of tagged IL-27 subunits (e.g., HA-tagged IL27p28) enables tracking of endogenous IL-27 production and secretion. Knock-in of reporter genes under the IL27 promoter allows live-cell monitoring of negative regulation.
Overexpression
Overexpression of negative regulators such as IL-10 or SOCS1 in macrophages can suppress IL-27 production, confirming their role. Conversely, overexpression of IL-27 subunits can test autocrine feedback.
How EDITGENE Supports negative regulation of interleukin-27 production Research
Researchers studying negative regulation of interleukin-27 production-related genes often need to determine whether a candidate gene is causally involved in suppressing IL-27. EDITGENE provides CRISPR-based cell models and screening services to accelerate this discovery.
Contact EDITGENE today to design your custom CRISPR model for negative regulation of interleukin-27 production research.
Frequently Asked Questions About negative regulation of interleukin-27 production
What is GO:0032711?
GO:0032711 is the Gene Ontology term for negative regulation of interleukin-27 production, describing any process that stops, prevents, or reduces the frequency, rate, or extent of IL-27 production.
What genes are involved in negative regulation of interleukin-27 production?
Key genes include IL27, EBI3, IL10, TGFB1, SOCS1, SOCS3, STAT3, and IL27RA, based on published studies.
How is IL-27 production negatively regulated?
IL-27 production is suppressed by anti-inflammatory cytokines like IL-10 and TGF-beta, by SOCS proteins, and through autocrine feedback via IL-27 receptor signaling.
Why is negative regulation of IL-27 important in sepsis?
In neonatal gram-negative sepsis, inhibition of IL-27 signaling improves outcomes by regulating chemokines and sustaining CXCR2 expression, highlighting the importance of controlling IL-27 levels.
Which cells produce IL-27?
IL-27 is produced by monocytes, neutrophils, and dendritic cells, among other innate immune cells.
What diseases are linked to IL-27 dysregulation?
IL-27 dysregulation is linked to bacterial sepsis, allergic rhinitis, and tuberculous pleural effusion.
How can CRISPR be used to study negative regulation of IL-27 production?
CRISPR knockout of candidate regulators, point mutations in IL27 promoter, and overexpression models can test causality in IL-27 suppression.
What methods measure IL-27 production?
ELISA, Luminex, RNA-seq, flow cytometry, and reporter assays are commonly used to quantify IL-27 production and its regulation.
Is IL-27 production autoregulated?
Yes, IL-27 can act as an endogenous constitutive repressor of human monocytes, indicating autocrine negative feedback.
What model organisms are used to study IL-27 regulation?
Murine models of neonatal sepsis and knockout mice for IL27, EBI3, and IL27RA are commonly used.
Conclusion
GO:0032711, negative regulation of interleukin-27 production, is a critical biological process that controls the intensity and duration of IL-27-mediated immune responses. Dysregulation of this process contributes to bacterial sepsis, allergic inflammation, and other diseases. Understanding the genes and pathways involved offers opportunities for therapeutic intervention. EDITGENE's CRISPR services, including knockout, point mutation, knock-in, overexpression, and library screening, provide researchers with powerful tools to dissect the negative regulation of IL-27 production and translate findings into clinical applications.
References
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- 2. Rinchai D et al.. 2012. Production of interleukin-27 by human neutrophils regulates their function during bacterial infection.. Eur J Immunol 42(12):3280-90 PMID: 22965735
- 3. Frangieh M et al.. 2020. IL-27: An endogenous constitutive repressor of human monocytes.. Clin Immunol 217:108498 PMID: 32531345
- 4. Povroznik JM et al.. 2025. The influence of interleukin-27 on metabolic fitness in a murine neonatal model of bacterial sepsis.. Am J Physiol Endocrinol Metab 328(3):E297-E310 PMID: 39810405
- 5. Li JP et al.. 2010. Interleukin-27 as a negative regulator of human neutrophil function.. Scand J Immunol 72(4):284-92 PMID: 20883313
- 6. Annamanedi M et al.. 2025. Inhibition of IL-27 signaling regulates chemokine levels and sustains CXCR2 receptor expression on mononuclear cells to improve disease outcomes during gram-negative neonatal sepsis.. Front Immunol 16:1653355 PMID: 40977737
- 7. Ouyang H et al.. 2020. Interleukin-27 Suppresses T Helper-17 Inflammation in Allergic Rhinitis.. Iran J Immunol 17(4):275-282 PMID: 33382384
- 8. Gan Y et al.. 2019. Exogenous intrapleural injection of interleukin-27 may improves outcome and prognosis in patients with tuberculous pleural effusion.. Med Hypotheses 131:109319 PMID: 31443751
