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

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

29262348

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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