Interleukin-11 receptor complex (IL-11R complex)

The Interleukin-11 (IL-11) receptor complex is a heteromeric signaling unit composed of the ligand-specific Interleukin-11 receptor alpha (IL-11RA) subunit and the common signal-transducing subunit glycoprotein 130 (gp130) [UniProt: P67051]. Upon binding of the IL-11 cytokine to IL-11RA, the complex recruits gp130 to form a functional signaling assembly, which activates intracellular cascades including the JAK/STAT3, MAPK/ERK, and PI3K/AKT pathways [PubMed: 29212808]. While historically recognized for its role in hematopoiesis and platelet production, recent evidence has established the IL-11 receptor complex as a primary driver of chronic fibrotic diseases in the heart, lungs, liver, and kidneys [PubMed: 32943551]. In these contexts, IL-11 signaling promotes the activation of fibroblasts into collagen-producing myofibroblasts and contributes to chronic inflammation. In oncology, the complex is implicated in tumor progression, metastasis, and the development of a pro-tumorigenic microenvironment [PubMed: 25103448]. Therapeutic approaches include the use of recombinant IL-11 as an agonist for thrombocytopenia and the development of neutralizing antibodies or small molecules to inhibit the complex for treating fibrosis and cancer [ClinicalTrials.gov].

Other names

IL-11R/gp130 complexInterleukin-11 receptor alpha/glycoprotein 130 complexIL11RA/CD130 complexIL-11R-alpha/gp130 complex

The IL-11 receptor complex is targeted through two primary modalities: agonism and antagonism. Agonists, such as recombinant IL-11 (Oprelvekin), bind to the IL-11RA/gp130 complex to stimulate megakaryocytopoiesis and increase platelet counts [FDA]. Conversely, therapeutic antagonists, including monoclonal antibodies like BI 765423 and small molecules like Lass601, disrupt the formation of the signaling complex or block ligand binding. This inhibition prevents the activation of downstream JAK/STAT3, ERK, and PI3K pathways, which are critical for myofibroblast differentiation and the progression of fibrotic diseases and certain malignancies [PubMed: 29212808, PubMed: 35145234].