interleukin-17A-mediated signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by interleukin-17A 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:jc, GOC:signaling]

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that plays a critical role in immune responses, particularly in the defense against extracellular bacteria and fungi. The IL-17A signaling pathway is initiated when IL-17A binds to its receptor, IL-17RA, which forms a heterodimer with IL-17RC. This binding event triggers a cascade of downstream signaling events, leading to the activation of transcription factors and the production of pro-inflammatory mediators. The key steps involved in the IL-17A-mediated signaling pathway are as follows:
1. **Ligand Binding:** IL-17A binds to its receptor complex, IL-17RA/IL-17RC, on the surface of target cells, such as epithelial cells, fibroblasts, and immune cells.
2. **Signal Transduction:** Ligand binding induces the recruitment of adaptor proteins, such as Act1, TRAF6, and TAK1, to the receptor complex. These adaptor proteins activate downstream signaling pathways, including the NF-κB pathway, MAPK pathway, and JNK pathway.
3. **Transcription Factor Activation:** Activation of these signaling pathways leads to the activation of transcription factors, such as NF-κB, AP-1, and STAT3. These transcription factors translocate to the nucleus and regulate the expression of target genes involved in inflammation and immunity.
4. **Production of Pro-inflammatory Mediators:** Transcriptional activation of target genes results in the production of various pro-inflammatory mediators, including chemokines (e.g., CXCL1, CXCL2, CXCL8), cytokines (e.g., TNF-α, IL-6), and antimicrobial peptides (e.g., defensins). These mediators contribute to the recruitment of immune cells, the induction of inflammation, and the elimination of pathogens.
5. **Immune Cell Recruitment and Activation:** Pro-inflammatory mediators attract and activate various immune cells, such as neutrophils, macrophages, and T cells. These cells contribute to the inflammatory response and the resolution of infection.

The IL-17A signaling pathway plays a critical role in host defense against pathogens. However, dysregulation of this pathway can contribute to the development of chronic inflammatory diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Understanding the mechanisms underlying IL-17A signaling is crucial for developing targeted therapies for these diseases.'
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Proteins (1)

Compounds (76)