GO:0032733 positive regulation of interleukin-10 production: Immune Regulation Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0032733 describes any process that activates or increases the frequency, rate, or extent of interleukin-10 (IL-10) production.
• IL-10 is a pleiotropic anti-inflammatory cytokine whose production is tightly regulated at transcriptional and post-transcriptional levels.
• GPR120 activation on CD4+ T cells promotes IL-10 production and inhibits colitis in mice.
• CPT1A-dependent metabolic reprogramming in macrophages increases IL-10 production and ameliorates acute lung injury.
• The KLF4/BIG1 axis regulates LPS-mediated neuroinflammation and migration in BV2 microglial cells via PI3K/Akt/NF-kB signaling.
• Dysregulated IL-10 production is implicated in sepsis, inflammatory bowel disease, and neuroinflammatory conditions [6,7].
Description
GO:0032733, positive regulation of interleukin-10 production, is a Gene Ontology biological process term that captures any mechanism that activates or increases the frequency, rate, or extent of interleukin-10 (IL-10) production. IL-10 is a key anti-inflammatory cytokine that limits tissue damage during infection and autoimmunity, and its production must be tightly controlled to avoid immunodeficiency or chronic inflammation. Understanding how IL-10 production is positively regulated is therefore central to immunology and to the development of therapies for inflammatory diseases. Experimental studies have identified diverse positive regulators of IL-10 production. For example, GPR120 activation on CD4+ T cells increases IL-10 production and suppresses colitis in mice. In macrophages, CPT1A-mediated metabolic reprogramming promotes IL-10 production and alleviates acute lung injury. In microglia, the KLF4/BIG1 axis modulates LPS-mediated neuroinflammation and migration through PI3K/Akt/NF-kB signaling, a pathway that intersects with IL-10 regulation. These findings illustrate that positive regulation of IL-10 production occurs in multiple cell types and disease contexts. Clinically, IL-10 production is elevated during septicaemia, and IL-10 deficiency alters intestinal epithelial responses to inflammatory signals. Glucocorticoids differentially regulate IL-10 and IL-12 in vitro, highlighting the pharmacological relevance of this process. Regulatory plasma cells are also a source of IL-10 that contributes to immune homeostasis. This article synthesizes the current understanding of GO:0032733, its mechanisms, key genes, disease links, and research methods.
positive regulation of interleukin-10 production At A Glance
| GO ID | GO:0032733 |
|---|---|
| GO term | positive regulation of interleukin-10 production |
| Ontology | biological_process |
| Synonym | activation of interleukin-10 production; positive regulation of IL-10 production; positive regulation of interleukin-10 biosynthetic process; positive regulation of interleukin-10 secretion; stimulation of interleukin-10 production; up regulation of interleukin-10 production; up-regulation of interleukin-10 production; upregulation of interleukin-10 production |
| Major function | Enhances the frequency, rate, or extent of IL-10 production, thereby modulating anti-inflammatory responses. |
| Related cytokine | Interleukin-10 (IL-10), a pleiotropic anti-inflammatory cytokine. |
| Cellular sources | CD4+ T cells, macrophages, microglia, regulatory plasma cells, and other immune cells [1,2,3,5]. |
| Disease relevance | Colitis, acute lung injury, neuroinflammation, septicaemia, and inflammatory bowel disease [1,2,3,6,7]. |
What Is GO:0032733?
GO:0032733 (positive regulation of interleukin-10 production) is defined as any process that activates or increases the frequency, rate, or extent of interleukin-10 production. In practical terms, it encompasses molecular events that boost the synthesis and secretion of IL-10, an anti-inflammatory cytokine, without specifying the upstream signal or cell type. The term is a child of 'regulation of interleukin-10 production' and is used to annotate gene products that experimentally enhance IL-10 output.
Why Is positive regulation of interleukin-10 production Important in Cell Biology?
Positive regulation of IL-10 production is critical because IL-10 is a master anti-inflammatory cytokine that prevents excessive tissue damage during immune responses. Dysregulation of IL-10 production is associated with inflammatory bowel disease, sepsis, and neuroinflammation [6,7]. Understanding the positive regulators of IL-10 production can reveal therapeutic targets for autoimmune and inflammatory diseases [1,2,3].
• IL-10 limits inflammation and tissue damage, making its positive regulation essential for immune homeostasis.
• GPR120-mediated IL-10 production in CD4+ T cells inhibits colitis, suggesting a therapeutic target for IBD.
• CPT1A-driven IL-10 production in macrophages ameliorates acute lung injury.
• KLF4/BIG1 regulates neuroinflammation and microglial migration via PI3K/Akt/NF-kB, intersecting with IL-10 regulation.
• IL-10 production is elevated during septicaemia, where it may contribute to immunoparalysis.
• IL-10 deficiency alters intestinal epithelial responses to inflammatory signals, highlighting its role in gut homeostasis.
• Glucocorticoids differentially regulate IL-10 and IL-12, showing pharmacological control of IL-10 production.
• Regulatory plasma cells are a source of IL-10 that supports immune tolerance.
What Happens During positive regulation of interleukin-10 production?
Initiation by Pattern Recognition and G Protein-Coupled Receptors
In simple terms: Certain receptors on immune cells sense signals and start a chain reaction that boosts IL-10 production.
Positive regulation of IL-10 production can be initiated by engagement of pattern recognition receptors (e.g., TLRs) or G protein-coupled receptors. For instance, GPR120 activation on CD4+ T cells increases IL-10 production and inhibits colitis in mice. In microglia, LPS stimulation triggers signaling through the KLF4/BIG1 axis, which modulates neuroinflammation and migration via PI3K/Akt/NF-kB. These initial signals set the stage for transcriptional and metabolic reprogramming that enhances IL-10 output.
Transcriptional and Post-Transcriptional Control
In simple terms: The cell turns up the dial on the IL-10 gene and stabilizes its RNA to make more protein.
The regulation of IL-10 expression occurs at multiple levels, including transcription, mRNA stability, and translation. Positive regulators often activate transcription factors that bind the IL10 promoter or enhancer regions. Post-transcriptional mechanisms, such as modulation of mRNA stability by RNA-binding proteins, also contribute to increased IL-10 production. This multilayered control ensures that IL-10 is produced only when needed.
Metabolic Reprogramming Supporting IL-10 Production
In simple terms: Changes in how cells use energy can promote the production of IL-10.
Metabolic pathways are increasingly recognized as positive regulators of IL-10 production. CPT1A-mediated fatty acid oxidation in macrophages induces metabolic and phenotypic alterations that increase IL-10 production and ameliorate acute lung injury. This demonstrates that cellular metabolism is coupled to the regulation of IL-10 synthesis.
Secretion and Feedback Amplification
In simple terms: Once made, IL-10 is released and can further influence the immune response.
IL-10 is secreted and acts on target cells to suppress inflammatory cytokine production. Positive regulation of IL-10 production includes processes that enhance secretion. In regulatory plasma cells, IL-10 secretion contributes to immune regulation. Elevated IL-10 production during septicaemia illustrates the systemic impact of enhanced secretion.
Key Genes Involved in GO:0032733 positive regulation of interleukin-10 production
The following genes and proteins are experimentally implicated in the positive regulation of interleukin-10 production.
| Gene | Major Role | Research Relevance |
|---|---|---|
| GPR120 (FFAR4) | Promotes IL-10 production in CD4+ T cells | Inhibits colitis in mice |
| CPT1A | Metabolic regulator that increases IL-10 production in macrophages | Ameliorates acute lung injury |
| KLF4 | Transcription factor regulating neuroinflammation and IL-10-related pathways | Modulates LPS-mediated microglial responses |
| BIG1 | Signaling protein in the KLF4/BIG1 axis | Regulates PI3K/Akt/NF-kB and migration in BV2 cells |
| IL10 | Encodes the anti-inflammatory cytokine IL-10 | Central to regulation of IL-10 production |
| IL10RA | IL-10 receptor alpha subunit | Mediates IL-10 signaling feedback |
| IL10RB | IL-10 receptor beta subunit | Mediates IL-10 signaling feedback |
| NF-kB | Transcription factor family involved in immune regulation | Modulated by KLF4/BIG1 axis |
| PI3K | Kinase in signaling pathways | Part of KLF4/BIG1 signaling |
| Akt | Kinase downstream of PI3K | Part of KLF4/BIG1 signaling |
| Glucocorticoid receptor (NR3C1) | Mediates glucocorticoid effects on IL-10 and IL-12 | Differential regulation in vitro |
| Regulatory plasma cell markers (e.g., CD138) | Source of IL-10 in immune regulation | Regulatory plasma cells |
How Is positive regulation of interleukin-10 production Regulated?
The positive regulation of IL-10 production is controlled by a network of signaling pathways and transcription factors. GPR120 activation enhances IL-10 production in CD4+ T cells. CPT1A-mediated metabolic reprogramming promotes IL-10 production in macrophages. The KLF4/BIG1 axis modulates PI3K/Akt/NF-kB signaling, which can influence IL-10 production in microglia. Glucocorticoids differentially regulate IL-10 and IL-12, indicating hormonal control. The regulation of IL-10 expression is also subject to post-transcriptional control.
positive regulation of interleukin-10 production and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| GPR120 | Colitis | CD4+ T cell-specific knockout or agonist treatment in mice |
| CPT1A | Acute lung injury | Macrophage-specific knockout or overexpression in mice |
| KLF4/BIG1 | Neuroinflammation | BV2 microglial cell line with knockdown or overexpression |
| IL10 | Inflammatory bowel disease | IL-10 knockout mice or intestinal epithelial cell models |
| Glucocorticoid receptor | Systemic inflammation | In vitro PBMC or monocyte cultures with glucocorticoid treatment |
Inflammatory Bowel Disease and Colitis
GPR120 activation on CD4+ T cells increases IL-10 production and inhibits colitis in mice, suggesting that positive regulation of IL-10 production is protective in colitis. IL-10 deficiency alters intestinal epithelial responses to inflammatory signals, further linking IL-10 to gut homeostasis.
Acute Lung Injury
CPT1A-mediated metabolic and phenotypic alterations in macrophages increase IL-10 production and ameliorate acute lung injury, indicating a protective role for positive regulation of IL-10 production in lung inflammation.
Neuroinflammation
The KLF4/BIG1 axis regulates LPS-mediated neuroinflammation and migration in BV2 microglial cells via PI3K/Akt/NF-kB signaling, a pathway that intersects with IL-10 regulation.
Sepsis and Systemic Inflammation
IL-10 production is elevated during septicaemia, where it may contribute to immunoparalysis. Glucocorticoids differentially regulate IL-10 and IL-12 in vitro, highlighting pharmacological modulation of IL-10 production in systemic inflammation.
From positive regulation of interleukin-10 production-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does GPR120 activation increase IL-10 production in CD4+ T cells? | GPR120 knockout mice or CD4+ T cell-specific knockout |
| Does CPT1A mediate metabolic reprogramming for IL-10 production? | Macrophage-specific CPT1A knockout or overexpression |
| How does KLF4/BIG1 regulate neuroinflammation via IL-10? | BV2 microglial cells with KLF4 or BIG1 knockdown |
| What is the effect of IL-10 deficiency on intestinal epithelium? | IL-10 knockout mice or intestinal epithelial cell lines |
| How do glucocorticoids differentially regulate IL-10 and IL-12? | Human PBMCs or monocytes treated with glucocorticoids |
| What is the role of regulatory plasma cells in IL-10 production? | B cell-specific knockout or reporter mice |
How to Study the positive regulation of interleukin-10 production Process
| Method | What It Measures | Typical Application |
|---|---|---|
| ELISA | IL-10 protein concentration | Quantify IL-10 in supernatants or serum [1,2,6] |
| Flow cytometry | Intracellular IL-10 and cell surface markers | Identify IL-10-producing cell subsets |
| RT-qPCR | IL10 mRNA levels | Assess transcriptional regulation |
| RNA-seq | Global transcriptome changes | Discover pathways co-regulated with IL-10 |
| Western blot | Phosphorylation of signaling proteins | Analyze PI3K/Akt/NF-kB activation |
| Seahorse assay | Extracellular acidification and oxygen consumption | Measure metabolic reprogramming |
| Reporter assay | IL10 promoter activity | Map regulatory elements |
Quantifying IL-10 Production
ELISA and flow cytometry are standard methods to measure IL-10 protein levels in cell culture supernatants and serum [1,2,6]. Intracellular cytokine staining allows identification of IL-10-producing cell types.
Transcriptional Analysis
RT-qPCR and RNA-seq can quantify IL10 mRNA levels and identify transcriptional changes in response to positive regulators. Reporter assays using the IL10 promoter can dissect regulatory elements.
Signaling Pathway Analysis
Western blotting and phospho-specific antibodies can assess activation of PI3K/Akt/NF-kB pathways in response to stimuli that enhance IL-10 production. Pharmacological inhibitors can confirm pathway involvement.
Metabolic Assays
Seahorse extracellular flux analysis and lipid oxidation assays can measure metabolic changes associated with increased IL-10 production, such as CPT1A-dependent fatty acid oxidation.
How CRISPR Can Be Used to Study GO:0032733 positive regulation of interleukin-10 production
Knockout
CRISPR knockout of candidate positive regulators (e.g., GPR120, CPT1A, KLF4) can determine whether they are required for IL-10 production. For example, GPR120 knockout mice show reduced IL-10 production and exacerbated colitis. CPT1A knockout in macrophages would test its role in metabolic support of IL-10 production.
Point Mutation
Point mutations can be introduced to disrupt specific phosphorylation sites or DNA-binding residues in transcription factors that regulate IL10. This allows precise mapping of signaling events, such as those in the KLF4/BIG1 axis.
Knock-in
Knock-in of reporter genes (e.g., GFP) into the IL10 locus enables real-time tracking of IL-10-producing cells. Knock-in of tagged IL-10 allows purification and analysis of secreted cytokine.
Overexpression
CRISPR activation (CRISPRa) or transgenic overexpression of candidate genes (e.g., GPR120, CPT1A) can boost IL-10 production and test sufficiency in disease models [1,2].
How EDITGENE Supports positive regulation of interleukin-10 production Research
Researchers studying positive regulation of interleukin-10 production-related genes often need to determine whether a candidate gene is causally involved in enhancing IL-10 output. EDITGENE provides CRISPR-based cell model services to accelerate this discovery.
Contact EDITGENE today to design your custom CRISPR model for positive regulation of interleukin-10 production research.
Frequently Asked Questions About positive regulation of interleukin-10 production
What is GO:0032733?
GO:0032733 is the Gene Ontology term for positive regulation of interleukin-10 production, defined as any process that activates or increases the frequency, rate, or extent of IL-10 production.
What genes are involved in positive regulation of interleukin-10 production?
Genes such as GPR120, CPT1A, KLF4, BIG1, and IL10 itself have been implicated in enhancing IL-10 production [1,2,3,4].
How is IL-10 production positively regulated?
IL-10 production is positively regulated by receptor signaling (e.g., GPR120), metabolic reprogramming (e.g., CPT1A), and transcription factors (e.g., KLF4), among other mechanisms [1,2,3].
What diseases are associated with dysregulated IL-10 production?
Dysregulated IL-10 production is associated with colitis, acute lung injury, neuroinflammation, septicaemia, and inflammatory bowel disease [1,2,3,6,7].
Which cell types produce IL-10?
IL-10 is produced by CD4+ T cells, macrophages, microglia, regulatory plasma cells, and other immune cells [1,2,3,5].
How can I study positive regulation of IL-10 production?
Common methods include ELISA, flow cytometry, RT-qPCR, RNA-seq, Western blotting, and metabolic assays [1,2,3,4].
What is the role of GPR120 in IL-10 production?
GPR120 activation on CD4+ T cells increases IL-10 production and inhibits colitis in mice.
How does CPT1A affect IL-10 production?
CPT1A-mediated metabolic reprogramming in macrophages increases IL-10 production and ameliorates acute lung injury.
What is the KLF4/BIG1 axis?
The KLF4/BIG1 axis regulates LPS-mediated neuroinflammation and migration in BV2 microglial cells via PI3K/Akt/NF-kB signaling, which intersects with IL-10 regulation.
Can glucocorticoids regulate IL-10 production?
Yes, glucocorticoids differentially regulate IL-10 and IL-12 in vitro, indicating pharmacological control of IL-10 production.
Conclusion
GO:0032733, positive regulation of interleukin-10 production, is a critical biological process that governs the anti-inflammatory cytokine IL-10. Research has identified multiple positive regulators, including GPR120, CPT1A, and the KLF4/BIG1 axis, which operate in diverse cell types and disease contexts [1,2,3]. Understanding these mechanisms offers therapeutic opportunities for inflammatory diseases such as colitis, acute lung injury, and neuroinflammation [1,2,3]. Continued investigation using CRISPR models and advanced methodologies will further elucidate the regulatory networks controlling IL-10 production.
References
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- 2. Wang M et al.. 2024. CPT1A-IL-10-mediated macrophage metabolic and phenotypic alterations ameliorate acute lung injury.. Clin Transl Med 14(8):e1785 PMID: 39090662
- 3. You Z et al.. 2022. The Novel KLF4/BIG1 Regulates LPS-mediated Neuro-inflammation and Migration in BV2 Cells via PI3K/Akt/NF-kB Signaling Pathway.. Neuroscience 488:102-111 PMID: 35090882
- 4. Gabryšová L et al.. 2014. The regulation of IL-10 expression.. Curr Top Microbiol Immunol 380:157-90 PMID: 25004818
- 5. Fillatreau S. 2015. Regulatory plasma cells.. Curr Opin Pharmacol 23:1-5 PMID: 25978519
- 6. Marchant A et al.. 1994. Interleukin-10 production during septicaemia.. Lancet 343(8899):707-8 PMID: 7907683
- 7. Papoutsopoulou S et al.. 2021. Impact of Interleukin 10 Deficiency on Intestinal Epithelium Responses to Inflammatory Signals.. Front Immunol 12:690817 PMID: 34220850
- 8. Visser J et al.. 1998. Differential regulation of interleukin-10 (IL-10) and IL-12 by glucocorticoids in vitro.. Blood 91(11):4255-64 PMID: 9596674
