UMMS Affiliation
Department of Medicine, Division of Infectious Diseases and Immunology
Publication Date
2017-12-19
Document Type
Article
Disciplines
Cell Biology | Cellular and Molecular Physiology | Immunology and Infectious Disease
Abstract
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.
Keywords
IL-4, IL-4 activated macrophages, M(IL-4), NCOR2, activation, human, inflammatory dendritic cells, inflammatory macrophages, macrophages, monocyte-derived dendritic cells, monocytes
Rights and Permissions
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
10.1016/j.immuni.2017.11.024
Source
Immunity. 2017 Dec 19;47(6):1051-1066.e12. doi: 10.1016/j.immuni.2017.11.024. Link to article on publisher's site
Journal/Book/Conference Title
Immunity
Related Resources
PubMed ID
29262348
Repository Citation
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.
https://escholarship.umassmed.edu/oapubs/3336
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Cell Biology Commons, Cellular and Molecular Physiology Commons, Immunology and Infectious Disease Commons
Comments
Full author list omitted for brevity. For the full list of authors, see article.