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PLoS One. 2018 Dec 7;13(12):e0208602. doi: 10.1371/journal.pone.0208602. eCollection 2018.

Transcriptional profiling identifies novel regulators of macrophage polarization.

Author information

1
The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
2
Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
3
The Bloomberg-Kimmel Institute for Cancer Immunotherapy, The Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
4
The Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, United States of America.
5
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America.

Abstract

Macrophages are key inflammatory immune cells that display dynamic phenotypes and functions in response to their local microenvironment. Major advances have occurred in understanding the transcriptional, epigenetic, and functional differences in various macrophage subsets by in vitro modeling and gene expression and epigenetic profiling for biomarker discovery. However, there is still no standardized protocol for macrophage polarization largely due to the lack of thorough validation of macrophage phenotypes following polarization. In addition, transcriptional regulation is recognized as a major mechanism governing differential macrophage polarization programs and as such, many genes have been identified to be associated with each macrophage subset. However, the functional role of many of these genes in macrophage polarization is still unknown. Moreover, the role of other regulatory mechanisms, such as DNA methylation, in macrophage polarization remains poorly understood. Here, we employed an optimized model of human M1 and M2 macrophage polarization which we used for large-scale transcriptional and DNA methylation profiling. We were unable to demonstrate a role for DNA methylation in macrophage polarization, as no significant changes were identified. However, we observed significant changes in the transcriptomes of M1 and M2 macrophages. Additionally, we identified numerous novel differentially regulated genes involved in macrophage polarization, including CYBB and DHCR7 which we show as important regulators of M1 and M2 macrophage polarization, respectively. Taken together, our improved in vitro human M1 and M2 macrophage model provides new understandings of the regulation of macrophage polarization and candidate macrophage biomarkers.

PMID:
30532146
PMCID:
PMC6286176
DOI:
10.1371/journal.pone.0208602
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests, all of which pertain to Elizabeth M. Jaffee: 1. Through a licensing agreement between JHU and Aduro Biotech, there is the potential to receive royalties for GVAX and Mesothelin, 2. Research funding through Aduro Biotech and Bristol-Myers Squibb, 3. Consulting activities: Adaptive Biotech, MedImmune and Genocea, 4. Scientific Advisory Board for Parker Institute for Cancer Immunology. This does not alter our adherence to PLOS One polices on sharing data and materials.

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