Cytokine signaling networks

Cytokine signaling networks are intricate systems of intercellular communication that regulate immune responses, inflammation, and hematopoiesis (Nature Reviews Immunology, 2018). These networks consist of various ligands, such as interleukins, interferons, and chemokines, which bind to specific transmembrane receptors to initiate intracellular signaling cascades (KEGG, 2023). A primary pathway involved is the Janus kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway, which translates extracellular signals into rapid gene expression changes (StatPearls, 2023). Proper functioning of these networks is crucial for host defense, but their dysregulation is linked to many diseases, including rheumatoid arthritis, psoriasis, and various cancers (PubMed, 2021). In autoimmune conditions, overactive cytokine signaling leads to chronic inflammation and progressive tissue damage. Therapeutic strategies often involve monoclonal antibodies that neutralize specific cytokines or their receptors, such as TNF inhibitors or IL-6 receptor antagonists (NIH, 2022). Small molecule inhibitors, particularly JAK inhibitors, are also used to block the intracellular transmission of these signals. Because these networks are pleiotropic and redundant, targeting them requires precision to avoid broad immunosuppression and associated safety risks like opportunistic infections.

Other names

Cytokine signaling pathwaysCytokine-cytokine receptor interactionCytokine cascadeImmune signaling networks

Drugs modulate these networks by neutralizing circulating cytokine ligands, blocking their cognate cell-surface receptors, or inhibiting downstream intracellular signaling components such as Janus kinases (JAKs) to prevent the transcription of pro-inflammatory genes.