Repository logo
 

Cellular Differentiation of Human Monocytes Is Regulated by Time-Dependent Interleukin-4 Signaling and the Transcriptional Regulator NCOR2.

Published version
Peer-reviewed

Change log

Authors

Sander, Jil 
Schmidt, Susanne V 
Cirovic, Branko 
Papantonopoulou, Olympia 

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.

Description

Keywords

IL-4, IL-4 activated macrophages, M(IL-4), NCOR2, activation, human, inflammatory dendritic cells, inflammatory macrophages, macrophages, monocyte-derived dendritic cells, monocytes, Cell Differentiation, Cell Lineage, Dendritic Cells, Gene Expression Profiling, Gene Expression Regulation, Granulocyte-Macrophage Colony-Stimulating Factor, Humans, Immunophenotyping, Interleukin-4, Macrophage Activation, Macrophage Colony-Stimulating Factor, Macrophages, Monocytes, Nuclear Receptor Co-Repressor 2, Primary Cell Culture, Signal Transduction, Time Factors, Transcription, Genetic

Journal Title

Immunity

Conference Name

Journal ISSN

1074-7613
1097-4180

Volume Title

47

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (204464/Z/16/Z)