interleukin-23-mediated signaling pathway

Definition

Target type: biologicalprocess

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, e.g. transcription. [GOC:nhn, GOC:signaling]

The interleukin-23 (IL-23)-mediated signaling pathway is a crucial component of the immune system, primarily involved in the regulation of inflammatory responses and the development of T helper 17 (Th17) cells. IL-23 is a heterodimeric cytokine composed of an IL-12p40 subunit shared with IL-12 and a unique IL-23p19 subunit. It is mainly produced by antigen-presenting cells, such as dendritic cells and macrophages, upon activation by various stimuli, including microbial products and inflammatory signals.

IL-23 exerts its biological effects by binding to its receptor, IL-23R, which forms a complex with IL-12Rβ1 on the surface of immune cells, primarily Th17 cells. Upon receptor binding, IL-23 triggers a cascade of intracellular signaling events:

1. **Signal transduction**: IL-23 receptor engagement activates the Janus kinase (JAK) family of tyrosine kinases, specifically JAK2 and TYK2.

2. **STAT3 activation**: Activated JAK kinases phosphorylate the signal transducer and activator of transcription 3 (STAT3) protein, leading to its dimerization and translocation to the nucleus.

3. **Gene transcription**: STAT3 dimers bind to specific DNA sequences in the promoter regions of target genes, inducing their transcription. These target genes include a variety of pro-inflammatory cytokines and chemokines, including IL-17A, IL-17F, IL-21, IL-22, and TNF-α.

4. **Th17 cell differentiation and function**: IL-23 plays a pivotal role in the differentiation and expansion of Th17 cells, a subset of T helper cells that are characterized by their production of IL-17A, IL-17F, and IL-22. Th17 cells contribute to inflammatory responses in various tissues, including the skin, gut, and lungs.

5. **Inflammatory responses**: The cytokines produced by Th17 cells, such as IL-17A, promote the recruitment and activation of neutrophils, macrophages, and other immune cells. These cells release pro-inflammatory mediators, such as chemokines and cytokines, further amplifying the inflammatory cascade.

6. **Immune homeostasis**: IL-23 also contributes to the maintenance of immune homeostasis by regulating the balance between pro- and anti-inflammatory responses.

Dysregulation of the IL-23 pathway can lead to various inflammatory and autoimmune diseases, including psoriasis, inflammatory bowel disease (IBD), rheumatoid arthritis, and multiple sclerosis. Therefore, targeting IL-23 signaling has become a promising therapeutic strategy for these conditions. Various therapeutic approaches are being developed to inhibit IL-23 production or block its interaction with its receptor, aiming to dampen inflammatory responses and alleviate disease symptoms.'
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Compounds (2)