Clarifying Dendritic cell terminology in the context of single-cell diversity — ASN Events
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  3. Clarifying Dendritic cell terminology in the context of single-cell diversity

Clarifying Dendritic cell terminology in the context of single-cell diversity (#109)

Sunrito Mitra 1 , the Dendritic cell community 2 , Johannes Mayer 1
  1. University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany, Mainz, RLP, Germany
  2. diverse locations, x

Dendritic cells (DC) are a heterogeneous and functionally plastic family of antigen-presenting cells that regulate immune homeostasis and disease. Since their discovery, multiple classification systems have been proposed to capture their diversity across tissues, developmental stages, and activation states. Early frameworks have classified DC based on anatomical location and surface markers. However, advances in flow cytometric phenotyping quickly identified overlapping marker expression across tissues, highlighting the limitations of location and tissue based classification systems. Subsequent findings led to an ontogeny-driven classification system, based on the discovery that common dendritic cell progenitor (CDP) defined conventional DC (cDC), which could further be subdivided into cDC1 and cDC2. While this framework improved conceptual consistency and is widely used to date, studies defining new populations of DC with diverse origins, call for an update to the DC classification system.

To address these limitations, we propose a four-tiered hierarchical terminology that uses lineages, subsets, phenotypes and states. This framework aligns with the sequential developmental progression of DC and prioritizes ontogeny as the primary organizing principle. The ‘lineage’ tier encompasses progenitors from bone marrow origin to committed precursors. The ‘subset’ tier defines DC that arise from a defined progenitor with a transcriptional program. The ‘phenotype’ tier captures stable adaptations to the microenvironment by DC ‘subsets’ that share the same progenitor, while the ‘state’ tier reflects dynamic functional programs associated with DC activation, tolerance, and immune modulation.

Our proposed classification system integrates established DC subsets, including cDC1 and cDC2, new populations, like mreg and RORγt⁺ DC, accommodates debated populations such as pDC-like cells and monocyte-derived DC and remains adaptable to future discoveries. Collectively, it provides a unified and flexible system for DC terminology in the context of single-cell diversity and is currently undergoing community review and discussion with many leaders in the field.