The interleukin-3 receptor alpha (IL3RA, also known as CD123) is a subunit of the interleukin-3 receptor complex, which plays a critical role in regulating hematopoiesis and immune responses. As a type I cytokine receptor, IL3RA combines with the beta common chain (βc) to form a high-affinity receptor for IL-3. a cytokine involved in the survival, proliferation, and differentiation of hematopoietic progenitor cells, dendritic cells, and eosinophils. CD123 is prominently expressed on plasmacytoid dendritic cells (pDCs) and certain hematopoietic malignancies, making it a biomarker of interest in both immunology and oncology.
IL3RA-targeting antibodies have emerged as promising tools for research and therapeutic applications. In cancer, CD123 overexpression is observed in acute myeloid leukemia (AML), blastic plasmacytoid dendritic cell neoplasm (BPDCN), and some lymphoid malignancies, driving antibody-based therapies such as antibody-drug conjugates (e.g., tagraxofusp) and bispecific antibodies. In autoimmune diseases like lupus, targeting CD123+ pDCs aims to modulate aberrant interferon-alpha production. Research-grade IL3RA antibodies are widely used to study receptor expression, signaling pathways (e.g., JAK/STAT activation), and cellular interactions. Challenges include balancing therapeutic efficacy with potential off-target effects due to CD123's expression on healthy hematopoietic stem cells. Ongoing studies explore engineered antibodies to enhance specificity and reduce toxicity.