negative regulation of interleukin-23 production

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate, or extent of interleukin-23 production. [GOC:mah]

Negative regulation of interleukin-23 (IL-23) production is a crucial process that helps maintain immune homeostasis and prevent excessive inflammation. IL-23 is a pro-inflammatory cytokine primarily produced by dendritic cells and macrophages in response to microbial stimuli. Its dysregulation can contribute to various inflammatory and autoimmune disorders, such as psoriasis, inflammatory bowel disease, and multiple sclerosis.

The negative regulation of IL-23 production involves a complex interplay of cellular and molecular mechanisms, including:

**1. Transcriptional Regulation:**

* **Suppressor of Cytokine Signaling (SOCS) proteins:** SOCS1 and SOCS3 are key inhibitors of IL-23 production. They bind to the IL-23 receptor complex, blocking downstream signaling pathways.
* **MicroRNAs (miRNAs):** Specific miRNAs, such as miR-146a and miR-155, have been shown to suppress IL-23 production by targeting its mRNA or the mRNA of its signaling components.
* **Transcription factors:** Transcription factors like STAT3 and NF-κB play a crucial role in IL-23 gene expression. Their activity can be negatively regulated by various mechanisms, including phosphorylation, ubiquitination, and interaction with inhibitory proteins.

**2. Post-translational Modification:**

* **Ubiquitination:** IL-23 can be targeted for degradation through ubiquitination, a process that marks proteins for proteasomal degradation.
* **Glycosylation:** Glycosylation of IL-23 can influence its stability and activity, potentially leading to reduced production.

**3. Cellular Mechanisms:**

* **Immunoregulatory cells:** Regulatory T cells (Tregs) and other immune cells can suppress IL-23 production by various mechanisms, including the release of anti-inflammatory cytokines, such as IL-10 and TGF-β.
* **Apoptosis:** Apoptosis, or programmed cell death, can eliminate cells producing IL-23, thereby reducing its production.
* **Exosomes:** Exosomes, small vesicles released by cells, can carry molecules that inhibit IL-23 production in recipient cells.

**4. Environmental Factors:**

* **Dietary components:** Certain dietary components, such as omega-3 fatty acids and probiotics, have been shown to modulate IL-23 production.
* **Lifestyle factors:** Factors like physical activity and stress levels can influence the immune response and IL-23 production.

**5. Therapeutic Interventions:**

* **Anti-IL-23 therapies:** Monoclonal antibodies targeting IL-23, such as ustekinumab and risankizumab, have been developed for the treatment of inflammatory disorders.
* **Immunomodulators:** Drugs that modulate the immune system, such as anti-TNF-α therapies, can indirectly affect IL-23 production.

In conclusion, negative regulation of IL-23 production is a multi-faceted process involving diverse cellular and molecular mechanisms. It is essential for maintaining immune homeostasis and preventing uncontrolled inflammation. Dysregulation of this process can contribute to the development of various inflammatory and autoimmune diseases.'
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Proteins (2)

Compounds (21)