CD123

CD123, also known as interleukin‑3 receptor alpha subunit (IL3RA), is a glycoprotein that functions as a component of the heterodimeric receptor for interleukin‑3. It is encoded by the IL3RA gene located on chromosome 1q23.1. The receptor complex is composed of the specific alpha chain (CD123) and a shared beta chain (βc), which is also part of the receptors for interleukin‑5 and interleukin‑9. Binding of IL‑3 to CD123 initiates downstream signaling pathways such as JAK/STAT, PI3K/AKT, and MAPK, promoting survival, proliferation, and differentiation of hematopoietic progenitor cells.

Expression of CD123 is found predominantly on plasmacytoid dendritic cells, regulatory T cells, megakaryocytes, and a subset of myeloid cells. In mast cells and eosinophils, CD123 plays a role in cytokine production and immune responses. Importantly, CD123 is overexpressed on leukemic blasts in acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN), making it a target for therapeutic interventions. Several antibody‑drug conjugates, bispecific T‑cell engagers, and CAR‑T cell therapies directed against CD123 are in preclinical or clinical development, aiming to selectively eliminate malignant cells while sparing normal hematopoiesis.

Genetic variants in IL3RA have been implicated in susceptibility to autoimmune conditions such as systemic lupus erythematosus and type 1 diabetes. Functional studies suggest that altered receptor signaling may influence immune regulation.

In summary, CD123 is a critical component of the interleukin‑3 receptor complex with key functions in hematopoiesis and immunity. Its aberrant expression in certain leukemias positions it as a promising therapeutic target, while genetic variation contributes to autoimmune disease risk.