Interleukin-6 receptor signaling complex (IL-6R signaling complex)

The Interleukin-6 (IL-6) receptor signaling complex is a multi-subunit protein assembly essential for mediating the pleiotropic effects of the IL-6 cytokine [1.1.1, 1.2.2]. It typically consists of a ligand-binding alpha subunit (IL-6R, CD126) and a signal-transducing beta subunit (gp130, CD130) [1.1.1, 1.2.1]. Upon IL-6 binding, the complex forms a hexameric structure that activates intracellular signaling pathways, primarily the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, as well as the MAPK and PI3K cascades [1.2.2, 1.2.3]. This signaling is critical for the immune response, hematopoiesis, and the acute-phase reaction [1.3.1, 1.5.2]. Dysregulation of this complex is a hallmark of various inflammatory and autoimmune diseases, such as rheumatoid arthritis and Castleman's disease, as well as cytokine release syndromes [1.3.1, 1.4.2]. Therapeutic strategies include monoclonal antibodies that block the IL-6 receptor or the cytokine itself, thereby preventing the assembly of the functional signaling complex and mitigating pathological inflammation [1.4.1, 1.4.5].

Other names

IL-6 receptor complexIL-6R/gp130 complexInterleukin-6 receptor subunit alpha/Glycoprotein 130 complexCD126/CD130 complexIL-6/IL-6R/gp130 hexameric complexInterleukin-6 receptor subunit alphaInterleukin-6 signal transducer

Monoclonal antibodies target the IL-6 receptor (alpha subunit) or the IL-6 ligand to prevent the formation of the functional hexameric signaling complex with gp130 [1.4.1, 1.4.5]. This blockade inhibits the activation of downstream Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways, as well as MAPK and PI3K/AKT signaling, thereby reducing the production of pro-inflammatory mediators and acute-phase proteins [1.2.2, 1.3.1].