CD123bright plasmacytoid predendritic cells: progenitors undergoing cell fate conversion?

Area of Science:

• Immunology
• Cell Biology
• Dendritic Cell Biology

Background:

• Plasmacytoid cells (PC) and CD1c(+) myeloid dendritic cells (DC) are human DC precursors expanded by Fms-like tyrosine kinase 3 ligand (FL).
• The lineage and phylogenetic origin of PC and their relationship to myeloid DC remain debated.
• It is unclear if PC and myeloid CD1c(+) DC represent distinct lineages.

Purpose of the Study:

• To investigate the phylogenetic affiliation and relationship of PC with myeloid DC.
• To determine if PC represent a distinct lineage or a cell population undergoing differentiation.
• To characterize the distinct subsets within the CD123(bright)HLA-DR(+) PC population.

Main Methods:

• Analysis of CD123(bright)HLA-DR(+) PC from FL-treated healthy volunteers.
• Flow cytometry to identify cell surface markers and phenotypes.
• Assessment of T-cell receptor (TCR) gene configuration.
• Evaluation of cytokine production and allostimulatory capacity.
• In vitro differentiation potential assessment.

Main Results:

• CD123(bright) PC can be divided into lymphoid-like and myeloid-like subsets.
• Lymphoid-like PC (majority) express lymphoid markers, have germline TCR loci, produce type I IFN, and differentiate into APC.
• Myeloid-like PC (minority) show an intermediate PC/myeloid DC phenotype, produce proinflammatory cytokines, and act as potent APCs without in vitro maturation.
• Lymphoid-like PC exhibit low allostimulatory capacity.

Conclusions:

• PC may not represent a distinct lineage but rather lymphoid cells undergoing in vivo cell fate conversion to a myeloid type.
• The findings challenge the notion of PC as a separate lineage, suggesting a dynamic differentiation pathway.
• PC exhibit plasticity, with subsets displaying either lymphoid or myeloid characteristics, impacting their function as APCs.