interleukin-27-mediated signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by interleukin-27 binding to a receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:add, GOC:BHF, GOC:mah, GOC:signaling]

Interleukin-27 (IL-27) is a heterodimeric cytokine composed of the p28 subunit (Epstein-Barr virus-induced gene 3, EBI3) and the p35 subunit (IL-27p28), which plays a crucial role in immune regulation. IL-27 signaling is initiated when IL-27 binds to its cognate receptor complex, consisting of the IL-27 receptor alpha (WSX-1) and the signal transducer and activator of transcription (STAT) 1-binding protein (gp130). This interaction triggers the activation of downstream signaling cascades, primarily involving the Janus kinase (JAK)-STAT pathway.

Upon ligand binding, the receptor complex undergoes dimerization, bringing together the associated JAK1 and Tyk2 kinases. These kinases then phosphorylate each other and the receptor subunits, creating docking sites for STAT1 and STAT3. Once recruited, STAT1 and STAT3 are phosphorylated by the JAK kinases, leading to their dimerization and translocation to the nucleus.

In the nucleus, the STAT1/STAT3 dimers bind to specific DNA sequences, known as interferon-stimulated response elements (ISREs), and activate the transcription of target genes. These genes encode a variety of proteins involved in immune responses, including interferon-gamma (IFN-γ), chemokines, and anti-apoptotic factors.

IL-27 signaling has diverse effects on immune cells, contributing to both pro-inflammatory and anti-inflammatory responses. It can promote the differentiation of T helper 1 (Th1) cells, which produce IFN-γ and play a crucial role in cell-mediated immunity. IL-27 can also suppress the differentiation of Th2 and Th17 cells, contributing to the control of allergic and autoimmune responses.

Furthermore, IL-27 has been implicated in the regulation of innate immunity. It can enhance the function of natural killer (NK) cells, promoting their cytotoxicity and cytokine production. IL-27 can also suppress the activity of dendritic cells, preventing excessive inflammation.

The IL-27 signaling pathway is tightly regulated, ensuring appropriate immune responses. Several mechanisms contribute to this regulation, including the expression levels of IL-27 and its receptor, the activity of JAK kinases, and the availability of STAT proteins. Dysregulation of IL-27 signaling can lead to various immune disorders, highlighting its importance in maintaining immune homeostasis.'
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Proteins (2)

Compounds (8)