Interleukin-6–Janus kinase–Signal transducer and activator of transcription signaling pathway (IL-6–JAK–STAT pathway)

The Interleukin-6–Janus kinase–Signal transducer and activator of transcription (IL-6–JAK–STAT) signaling pathway is a critical mediator of the inflammatory response and cellular homeostasis. The cascade begins when IL-6 binds to its receptor (IL-6R), leading to the recruitment of the signal-transducing subunit gp130 and subsequent activation of associated Janus kinases (JAK1, JAK2, and TYK2). These kinases phosphorylate STAT3, which then dimerizes and translocates to the nucleus to regulate the transcription of genes involved in cell growth, survival, and the acute phase response. Dysregulation of this pathway is a hallmark of numerous autoimmune diseases and malignancies, where chronic activation drives pathological inflammation and tumor progression. Consequently, this axis is a major therapeutic focus, with approved drugs targeting the ligand (IL-6), the receptor (IL-6R), or the intracellular kinases (JAKs) to treat conditions ranging from rheumatoid arthritis to cytokine release syndrome.

Other names

IL-6/JAK/STAT3 axisInterleukin-6 signaling cascadeIL-6–JAK–STAT signaling axis

Drugs targeting this pathway act by neutralizing the IL-6 ligand, blocking the IL-6 receptor (IL-6R/gp130), or inhibiting the intracellular Janus kinases (JAKs) to prevent the phosphorylation and activation of STAT transcription factors.