Tissue clonality of dendritic cell subsets and emergency DCpoiesis revealed by multicolor fate mapping of DC progenitors

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Science Immunology  01 Mar 2019:
Vol. 4, Issue 33, eaaw1941
DOI: 10.1126/sciimmunol.aaw1941

Dendritic cell dynamics

Conventional dendritic cells (cDCs) are critical to innate immunity and orchestrating adaptive T cell responses. cDCs originate from a common precursor and can be delineated into different subtypes. Cabeza-Cabrerizo et al. use multicolor fate mapping in mice to show that precursor cDCs enter tissue, differentiate into a single subtype, and proliferate as clones of sister cDCs under steady-state conditions. Viral infection causes a rapid influx of cDCs into infected tissue, and these cells differentiate into tissue-resident cDCs and dilute preexisting cDC clones. These results provide insight into cDC dynamics in tissues and how infection can cause rapid changes in cDC population frequencies.


Conventional dendritic cells (cDCs) are found in all tissues and play a key role in immune surveillance. They comprise two major subsets, cDC1 and cDC2, both derived from circulating precursors of cDCs (pre-cDCs), which exited the bone marrow. We show that, in the steady-state mouse, pre-cDCs entering tissues proliferate to give rise to differentiated cDCs, which themselves have residual proliferative capacity. We use multicolor fate mapping of cDC progenitors to show that this results in clones of sister cDCs, most of which comprise a single cDC1 or cDC2 subtype, suggestive of pre-cDC commitment. Upon infection, a surge in the influx of pre-cDCs into the affected tissue dilutes clones and increases cDC numbers. Our results indicate that tissue cDCs can be organized in a patchwork of closely positioned sister cells of the same subset whose coexistence is perturbed by local infection, when the bone marrow provides additional pre-cDCs to meet increased tissue demand.

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