IL11RA

Interleukin-11 receptor subunit alpha (IL11RA), also designated CDw128a or IL-11Rα, is a transmembrane glycoprotein that forms the ligand-binding subunit of the functional IL-11 receptor complex. Upon IL-11 binding, IL11RA dimerizes with glycoprotein 130 (gp130) to activate JAK/STAT, MAPK, and PI3K/AKT signaling cascades, regulating cellular proliferation, differentiation, and apoptosis. This receptor is critically involved in hematopoiesis, osteoclastogenesis, and mucosal epithelial regeneration. Its signaling intersects with pathways governing extracellular matrix remodeling and inflammatory responses, including TGF-β crosstalk.
Dysregulated IL11RA signaling associates with myelofibrosis, osteoporosis, and epithelial-to-mesenchymal transition in metastatic cancers. Emerging evidence implicates IL11RA overexpression in fibrotic disorders such as pulmonary fibrosis and Crohn's disease. Therapeutic strategies targeting IL-11/IL11RA axis include neutralizing antibodies (e.g., X203) and small-molecule inhibitors disrupting STAT3 phosphorylation, with several candidates in preclinical evaluation for fibrosis and oncology indications. A phase I trial (NCT04861506) recently assessed anti-IL11 agents in solid tumors, demonstrating preliminary safety profiles.