negative regulation of T-helper 17 cell differentiation

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of T-helper 17 cell differentiation. [GOC:BHF, GOC:mah]

Negative regulation of T-helper 17 (Th17) cell differentiation is a complex process that involves multiple signaling pathways and transcription factors. Th17 cells are a subset of CD4+ T cells that produce pro-inflammatory cytokines, such as IL-17A, IL-17F, and IL-22, which play critical roles in host defense against extracellular pathogens and in the pathogenesis of autoimmune diseases.

The differentiation of naïve CD4+ T cells into Th17 cells is initiated by signals from antigen-presenting cells (APCs), such as dendritic cells and macrophages. These signals include:

* **IL-6:** IL-6 is a pro-inflammatory cytokine that activates the STAT3 signaling pathway. STAT3 is a transcription factor that promotes the expression of IL-17A, IL-17F, and other Th17-associated genes.
* **TGF-β:** TGF-β is a pleiotropic cytokine that can induce the differentiation of naïve CD4+ T cells into both Th17 and regulatory T (Treg) cells. In the presence of IL-6, TGF-β promotes Th17 differentiation, while in the absence of IL-6, it promotes Treg differentiation.
* **IL-23:** IL-23 is a cytokine that is produced by APCs after activation. It acts on differentiated Th17 cells to maintain their stability and promote their effector function.
* **IL-1β:** IL-1β is a pro-inflammatory cytokine that can synergize with IL-6 and TGF-β to enhance Th17 differentiation.

Once Th17 cells are differentiated, they can be negatively regulated by a variety of mechanisms, including:

* **Treg cells:** Treg cells suppress the differentiation and function of Th17 cells by producing immunosuppressive cytokines, such as IL-10 and TGF-β.
* **IL-27:** IL-27 is a cytokine that can inhibit the differentiation of Th17 cells by activating STAT1 signaling pathway. STAT1 is a transcription factor that inhibits the expression of Th17-associated genes.
* **IL-35:** IL-35 is a cytokine that is produced by Treg cells and can suppress the differentiation and function of Th17 cells.
* **Aryl hydrocarbon receptor (AhR):** AhR is a transcription factor that is activated by environmental ligands, such as dietary polycyclic aromatic hydrocarbons. AhR can suppress the differentiation and function of Th17 cells.
* **MicroRNAs (miRNAs):** miRNAs are small non-coding RNAs that can regulate gene expression. Several miRNAs, such as miR-21 and miR-146a, have been shown to suppress Th17 differentiation.
* **Other cytokines:** Other cytokines, such as IL-2, IL-4, and IL-12, can also inhibit the differentiation of Th17 cells by promoting the differentiation of other T cell subsets.

Negative regulation of Th17 differentiation is essential for maintaining immune homeostasis and preventing autoimmunity. Dysregulation of Th17 cell differentiation can contribute to the development of autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease.'
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Proteins (1)

Compounds (7)