Dendritic Cells

RESEARCH HIGHLIGHTS

Further investigation of these mice DENDRITIC CELLS showed that cDCs in non-lymphoid tissues, including the lungs, intestines and kidneys, can be specifically Tracing the origins of cDCs identified by their DNGR1 expression history. In the lungs, CD103+ cells, CD103–CD11b– cells and CD11b+ The classification of macrophages and common DC precursors (CDPs). cells were labelled with YFP, even dendritic cells (DCs) has mainly been To test the differentiation potential though the CD103–CD11b– and based on cell morphology, phenotype of these cells, lineage-negative CD11b+ cell subsets lacked DNGR1 and/or select functional attributes. CD115+DNGR1+ bone marrow cells expression. By contrast, pDCs and However, many of these markers were transferred to congenic mice. CD64+ cells (which have been argued are not unique to a specific cell type, In contrast with unfractionated bone to represent monocyte progeny) which has resulted in much debate marrow, which gave rise to a variety were inefficiently labelled with YFP. as to whether a given mononuclear of lymphoid and myeloid lineages, Similarly, in the small intestine, phagocyte should be classified as a lineage-negative CD115+DNGR1+ CD11b–CD103+ cells, CD11b+CD103+ DC or a macrophage. Reporting in bone marrow cells almost exclusively cells and CD11b+CD103– cells (a cell Cell, Reis e Sousa and colleagues show generated CD11c+MHC class II+ subset which has previously been that the precursors of conventional cDCs, but not pDCs. This suggests suggested to arise from monocytes) DCs (cDCs) in mice are marked by that DNGR1 expression marks pre- all expressed YFP, which indicates that dendritic cell natural killer lectin cursor cells that have a cDC-restricted they descend from CDPs. By contrast, group receptor 1 (DNGR1; encoded a model... differentiation potential. Of note, on monocyte-derived CD11clowCD64+ by CLEC9A), and they describe a which the basis of the data in the paper, the cells were poorly labelled with YFP. model in which these cells and their facilitates the authors suggested that the acronym Interestingly, CD64+ cells specifically progeny are genetically labelled, which identification CDPs should therefore be defined as in the kidneys were also labelled facilitates the identification of cDCs conventional DC precursors. with YFP, which suggests that the in mice on the basis of ontogeny of cDCs in mice Next, the authors generated expression of CD64 does not dif- rather than phenotype or function. on the basis mice in which DNGR1-expressing ferentiate between CDP-derived and Previous studies have shown of ontogeny cells and their progeny are indel- monocyte-derived cells in this tissue that plasmacytoid DCs (pDCs) ibly marked with enhanced yellow site. Further analysis showed that and specific cDC subsets express rather than fluorescent protein (YFP), termed CD64+CD11blowF4/80hi kidney cells DNGR1. Now the authors show that phenotype or Clec9a+/creRosa+/EYFP mice. As had phenotypic and functional DNGR1 is also expressed by bone function expected, the expression of YFP in properties that are typical of cDCs. marrow progenitor cells that pheno- these mice was restricted to CDPs, Finally, Clec9a+/creRosa+/EYFP mice typically resemble to resident CD8α+ and CD11b+ were shown to faithfully trace cDC subsets in the spleen and CDP-derived cells, but not monocyte- skin-draining lymph nodes, and to derived cells that resemble cDCs, + C migratory CD103 cDCs in the skin. during inflammation following IS D TO No YFP expression was observed in infection with Listeria monocytogenes HO + /P CD169 metallophilic macrophages, or following dextran sulphate sodium Y T T hi E in Langerhans cells, or in LY6C and treatment to induce colitis. G LY6Clow monocytes. Of note, pDCs So, Clec9a+/creRosa+/EYFP mice (SIGLEC-H+B220+) expressed only represent an in vivo model to identify low levels of YFP, which, together cDCs on the basis of their onto with the results of the transfer study genetic descendence from a commit- described above, suggests that these ted precursor cell and have been used cells arise from a distinct pDC- in this study to confirm that cDCs are specific precursor cell. However, an independent leukocyte lineage. CD8α+CD205– cells, which have Olive Leavy

previously been reported to resemble ORIGINAL RESEARCH PAPER Schraml, B. U. pDCs, expressed high levels of YFP, et al. Genetic tracing via DNGR-1 expression which suggests that they arise from history defines dendritic cells as a hematopoietic lineage. Cell 154, 843–858 (2013) CDPs.

NATURE REVIEWS | IMMUNOLOGY VOLUME 13 | OCTOBER 2013