Tissue clonality of dendritic cell subsets and emergency DCpoiesis revealed by multicolor fate mapping of DC progenitors
journal contributionposted on 11.12.2019, 18:02 authored by Mar Cabeza-Cabrerizo, Janneke van Blijswijk, Stephan Wienert, Daniel Heim, Robert P Jenkins, Probir Chakravarty, Neil Rogers, Bruno Frederico, Sophie Acton, Evelyne Beerling, Jacco van Rheenen, Hans Clevers, Barbara U Schraml, Marc Bajénoff, Michael Gerner, Ronald N Germain, Erik Sahai, Frederick Klauschen, Caetano Reis e Sousa
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.