Cabeza-Cabrerizo and van Blijswijk et al. showed that after pre-cDCs leave the bone marrow, circulate, and enter local tissue, they proliferate on site and give rise to differentiated cDCs, which also maintain residual proliferative capacity. Multicolor fate mapping showed that cDCs form a patchwork within tissues, with clones accumulating in local clusters that largely consist of the same subset (cDC1 or cDC2), suggesting that incoming pre-DCs may have a predetermined lineage. In the context of infection, an “emergency” influx of pre-cDCs perturbs this patchwork in affected tissues, diluting clones and increasing cDC numbers.
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.
Author Info: (1) Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. caetano@crick.ac.uk mar.cabeza-cabrerizo@crick.ac.uk jannekevanblijswijk@gmail.com fr
Author Info: (1) Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. caetano@crick.ac.uk mar.cabeza-cabrerizo@crick.ac.uk jannekevanblijswijk@gmail.com frederick.klauschen@charite.de. (2) Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. caetano@crick.ac.uk mar.cabeza-cabrerizo@crick.ac.uk jannekevanblijswijk@gmail.com frederick.klauschen@charite.de. (3) Institute of Pathology, Charite University Medicine Berlin, Chariteplatz 1, D-10117 Berlin, Germany. (4) Institute of Pathology, Charite University Medicine Berlin, Chariteplatz 1, D-10117 Berlin, Germany. (5) Tumour Cell Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. (6) Bioinformatics, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. (7) Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. (8) Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. (9) Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. (10) Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, Netherlands. (11) Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, Netherlands. (12) Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, Netherlands. (13) Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. (14) Aix-Marseille University Centre, National de la Recherche Scientifique (CNRS), Institut National de la Sante et de la Recherche Medicale (INSERM), Centre d'Immunologie de Marseille-Luminy (CIML), Marseille, France. (15) Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. (16) Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. (17) Tumour Cell Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. (18) Institute of Pathology, Charite University Medicine Berlin, Chariteplatz 1, D-10117 Berlin, Germany. caetano@crick.ac.uk mar.cabeza-cabrerizo@crick.ac.uk jannekevanblijswijk@gmail.com frederick.klauschen@charite.de. (19) Immunobiology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. caetano@crick.ac.uk mar.cabeza-cabrerizo@crick.ac.uk jannekevanblijswijk@gmail.com frederick.klauschen@charite.de.
