Interleukin-6 receptor (IL-6R (primary receptor), gp130 (signal transducer), IL-6 signaling (pathway))

The Interleukin-6 signaling pathway is initiated when IL-6 binds to the IL-6 receptor (IL-6R), composed of an IL-6-specific binding chain (IL-6Rα/CD126) and the signal-transducing glycoprotein 130 (gp130/CD130)[2][1]. Upon ligand engagement, this receptor complex assembles into a hexameric structure on the cell surface, activating the intracellular JAK/STAT signaling cascade, as well as MAPK and PI3K pathways[1][6]. These signaling events regulate the transcription of target genes involved in immune responses, inflammation, cell survival, proliferation, and regeneration[1][6][4]. Two principal modes of IL-6 signaling are distinguished: classical signaling (via membrane-bound IL-6R) and trans-signaling (via soluble IL-6R), allowing IL-6 to act upon a broader range of cell types[1][4][3]. The pathway is a key hub in mediating inflammatory diseases, autoimmunity, oncogenesis, and host defense, making the IL-6 receptor complex a critical therapeutic target[5][4][6]. Drugs inhibiting IL-6 or its receptor are established treatments for inflammatory and autoimmune conditions, with additional roles in cancer and infectious diseases[5][1].

Other names

IL-6 receptorIL-6Rα or CD126 (IL-6-binding chain)gp130 or CD130 (signal transducer)sIL-6R (soluble IL-6 receptor)IL6ST (gene encoding gp130)

Inhibition of IL-6 binding to IL-6 receptor - Blockade of IL-6R activation, preventing downstream JAK/STAT, MAPK, and PI3K signaling - Neutralization of circulating IL-6