Interleukin-11 receptor alpha with gp130 co-receptor (IL-11RA/gp130 complex)

The Interleukin-11 receptor alpha (IL-11RA) with gp130 co-receptor is a signaling complex belonging to the IL-6 family of cytokine receptors. IL-11 first binds to its specific alpha subunit, IL-11RA, which then recruits the signal-transducing subunit gp130 (also known as CD130 or IL6ST) to form a high-affinity hexameric complex. This assembly triggers downstream signaling pathways, most notably the JAK/STAT3 and MEK/ERK cascades, which regulate cell proliferation, survival, and mesenchymal transition. While historically associated with hematopoiesis and platelet production, recent research has identified the IL-11/IL-11RA/gp130 axis as a primary driver of fibrosis and chronic inflammation across multiple organs, including the lungs, liver, and heart. In pathological states, overactive IL-11 signaling promotes the transformation of fibroblasts into myofibroblasts and contributes to the progression of various cancers and age-related diseases. Therapeutic strategies targeting this complex include recombinant IL-11 (Oprelvekin) for thrombocytopenia, as well as novel monoclonal antibodies (e.g., LASN01, BI 765423) designed to block the pro-fibrotic and pro-inflammatory effects of the pathway in conditions like idiopathic pulmonary fibrosis and NASH.

Other names

IL-11R subunit alphaIL-11R-alphaIL11RAgp130IL6STCD130Interleukin-11 receptor subunit alphaInterleukin-6 signal transducer

Agonism (e.g., Oprelvekin) involves binding to IL-11RA and recruiting gp130 to activate JAK/STAT3 and ERK signaling for platelet production. Antagonism (e.g., LASN01, BI 765423) involves blocking IL-11 binding to IL-11RA or preventing the recruitment of gp130, thereby inhibiting pro-fibrotic and pro-inflammatory signaling cascades such as JAK/STAT3 and MEK/ERK.