GO:0038155 interleukin-23-mediated signaling pathway

GO:0038155, the interleukin-23-mediated signaling pathway, is a biological process ontology term that describes the molecular cascade triggered when the cytokine interleukin-23 (IL-23) binds its receptor on the surface of a target cell, culminating in regulation of downstream cellular processes such as transcription. IL-23 is a heterodimeric cytokine composed of a p19 subunit and a p40 subunit, and it signals through a receptor complex that activates intracellular kinases and transcription factors. Because this pathway controls the expansion and effector function of Th17 cells, it sits at the center of immune-mediated inflammatory responses. For researchers, GO:0038155 provides a standardized framework to annotate genes, interpret transcriptomic and proteomic datasets, and design mechanistic experiments. Pathway enrichment tools frequently map differentially expressed genes to this term when studying autoimmune and inflammatory conditions. The term is also a practical anchor for CRISPR-based functional genomics, because perturbing individual components of the pathway allows causal testing of receptor-proximal versus downstream events. This article summarizes the QuickGO definition, the major stages of the pathway, the key genes and proteins involved, disease associations, and the experimental methods, including CRISPR cell models, that are used to study interleukin-23-mediated signaling.

According to the QuickGO definition, GO:0038155 is the series of molecular signals initiated by interleukin-23 binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, for example transcription. In other words, the term covers the entire sequence from ligand-receptor engagement at the plasma membrane through intracellular signal transduction to a functional cellular outcome. It is classified under biological_process and is also known by the synonyms IL-23-mediated signaling pathway and interleukin-23-mediated signalling pathway.

GO:0038155 is important because interleukin-23-mediated signaling is a central amplifier of inflammatory immune responses and a validated therapeutic axis. The pathway drives Th17 cell expansion and effector function, which are implicated in autoimmune and inflammatory pathology. Network pharmacology studies of anti-inflammatory interventions repeatedly identify IL-23 signaling among the key modulated pathways, underscoring its relevance as a mechanistic and translational target. For basic researchers, the term offers a precise annotation unit for multi-omics data, while for translational scientists it provides a defined set of genes and steps that can be perturbed with CRISPR to test causality.

The following genes and proteins represent the principal components and context-dependent modifiers associated with interleukin-23-mediated signaling pathway (GO:0038155), based on the verified literature.

Regulation of interleukin-23-mediated signaling pathway (GO:0038155) occurs at multiple levels, including ligand availability, receptor expression, and intracellular feedback. The pathway is modulated by the broader inflammatory environment, as illustrated by crosstalk with prostaglandin E2-EP4 signaling, which promotes Th1 cell differentiation and Th17 cell expansion and thereby influences the cellular context in which IL-23 acts. Network pharmacology analyses of anti-inflammatory interventions identify IL-23 signaling among the pathways whose activity is altered by treatment, indicating that the pathway is responsive to pharmacological modulation. These observations support the view that GO:0038155 is not a fixed linear cascade but a regulated process whose output depends on the cytokine milieu and the activation state of the target cell.

Interleukin-23-mediated signaling is a central driver of Th17 cell expansion, a process strongly associated with immune-mediated inflammatory pathology. Because the pathway amplifies inflammatory T cell responses, it is a focus of therapeutic strategies aimed at dampening chronic inflammation. Network pharmacology studies of anti-inflammatory formulas identify IL-23 signaling among the key modulated pathways, supporting its disease relevance.

The expansion and maintenance of Th17 cells downstream of IL-23 signaling link GO:0038155 to autoimmune conditions characterized by excessive inflammatory T cell activity. Crosstalk with other inflammatory mediators, such as prostaglandin E2-EP4 signaling, can further shape the autoimmune response. This makes the pathway a rational target for mechanistic studies in autoimmune disease models.

Sustained activation of IL-23-mediated signaling can contribute to tissue-damaging inflammation through the effector molecules produced by expanded Th17 cells. The pathway therefore represents a node where cytokine signals translate into effector functions relevant to tissue pathology. Experimental models that perturb pathway components can help define which steps are most amenable to intervention.

RNA sequencing after cytokine stimulation can identify the transcriptional output of GO:0038155 and reveal which genes depend on specific pathway components. Comparing wild-type and CRISPR-knockout cells allows causal attribution of gene expression changes to the pathway. Pathway enrichment of the resulting data frequently maps to interleukin-23-mediated signaling.

Network pharmacology approaches integrate compound-target and pathway databases to identify signaling cascades modulated by treatment. Such analyses have identified IL-23 signaling among the pathways affected by anti-inflammatory interventions. These methods are useful for generating hypotheses that can then be tested with CRISPR models.

T cell differentiation assays measure the expansion of Th17 cells as a functional readout of IL-23-mediated signaling. These assays can be combined with genetic perturbation to test the contribution of individual pathway genes. Crosstalk with other inflammatory mediators, such as prostaglandin E2-EP4 signaling, can be assessed in the same system.

Immunoblotting and phospho-specific assays can measure activation of kinases and transcription factors downstream of receptor engagement. These readouts complement transcriptomic data by capturing the proximal signaling events of GO:0038155. Combining protein-level and RNA-level measurements provides a more complete picture of pathway activity.

Researchers studying interleukin-23-mediated signaling pathway-related genes often need to determine whether a candidate gene is causally involved in pathway output, which requires precise genetic perturbation rather than correlative observation. EDITGENE provides the cell-model and screening tools needed to move from candidate lists to mechanistic conclusions.

GO:0038155, interleukin-23-mediated signaling pathway, is a well-defined biological process that connects cytokine-receptor engagement to transcriptional regulation and immune cell expansion. Its central role in Th17 cell biology and inflammatory disease makes it a high-value target for mechanistic and translational research. By combining pathway annotation with CRISPR-based perturbation and multi-omics readouts, researchers can build causal models of how this pathway operates in health and disease.