Dendritic cell precursor receptors

Dendritic cell precursor receptors refer to a diverse set of surface molecules expressed on hematopoietic progenitor cells committed to the dendritic cell (DC) lineage, including common dendritic cell precursors (CDPs) and pre-DCs [1, 2]. Key members of this group include Fms-like tyrosine kinase 3 (FLT3/CD135), the C-type lectin receptor CLEC9A (DNGR-1), and the interleukin-3 receptor alpha chain (CD123) [3, 4]. These receptors are essential for the regulation of DC development (cDCpoiesis), governing the survival, proliferation, and differentiation of precursors into functional DC subsets like cDC1, cDC2, and plasmacytoid DCs (pDCs) [1, 5]. The term is considered a broad classification rather than a single molecular target, as it encompasses multiple distinct proteins with unique signaling pathways [1, 2]. Therapeutically, these receptors are significant targets in oncology and immunology. FLT3 signaling is often manipulated using ligands to expand DC populations for cancer vaccines or using inhibitors to treat FLT3-mutated leukemias [3]. CD123 is a primary target for treating blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare and aggressive hematologic malignancy derived from pDC precursors [4]. Additionally, receptors like CLEC9A are being explored for targeted delivery of antigens to DC precursors to enhance vaccine efficacy [1]. Safety concerns associated with targeting these receptors include capillary leak syndrome, particularly with CD123-directed therapies, and myelosuppression with FLT3 inhibitors [3, 4].

Other names

Dendritic cell progenitor receptorsDC precursor receptorscDC precursor receptorspDC precursor receptorsDendritic cell-targeting receptors

Activation of dendritic cell development via FLT3 agonism; inhibition of precursor proliferation via FLT3 tyrosine kinase inhibition; targeted depletion of malignant precursors via CD123-directed cytotoxins [3, 4].