Department of Medicine, Division of Infectious Diseases and Immunology
Cell Biology | Cellular and Molecular Physiology | Immunology and Infectious Disease
Human in vitro generated monocyte-derived dendritic cells (moDCs) and macrophages are used clinically, e.g., to induce immunity against cancer. However, their physiological counterparts, ontogeny, transcriptional regulation, and heterogeneity remains largely unknown, hampering their clinical use. High-dimensional techniques were used to elucidate transcriptional, phenotypic, and functional differences between human in vivo and in vitro generated mononuclear phagocytes to facilitate their full potential in the clinic. We demonstrate that monocytes differentiated by macrophage colony-stimulating factor (M-CSF) or granulocyte macrophage colony-stimulating factor (GM-CSF) resembled in vivo inflammatory macrophages, while moDCs resembled in vivo inflammatory DCs. Moreover, differentiated monocytes presented with profound transcriptomic, phenotypic, and functional differences. Monocytes integrated GM-CSF and IL-4 stimulation combinatorically and temporally, resulting in a mode- and time-dependent differentiation relying on NCOR2. Finally, moDCs are phenotypically heterogeneous and therefore necessitate the use of high-dimensional phenotyping to open new possibilities for better clinical tailoring of these cellular therapies.
IL-4, IL-4 activated macrophages, M(IL-4), NCOR2, activation, human, inflammatory dendritic cells, inflammatory macrophages, macrophages, monocyte-derived dendritic cells, monocytes
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Copyright 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
DOI of Published Version
Immunity. 2017 Dec 19;47(6):1051-1066.e12. doi: 10.1016/j.immuni.2017.11.024. Link to article on publisher's site
Sander, Jil; Latz, Eicke; and Schlitzer, Andreas, "Cellular Differentiation of Human Monocytes Is Regulated by Time-Dependent Interleukin-4 Signaling and the Transcriptional Regulator NCOR2" (2017). Open Access Articles. 3336.
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This work is licensed under a Creative Commons Attribution 4.0 License.