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DNA methylation in the promoters of PD-L1, MMP9, ARG1, galectin-9, TIM-3, VISTA and TGF-β genes in HLA-DR– myeloid cells, compared with HLA-DR+ antigen-presenting cells
- Source :
- Epigenetics, article-version (VoR) Version of Record
- Publication Year :
- 2020
- Publisher :
- Taylor & Francis, 2020.
-
Abstract
- Myeloid cells, including antigen-presenting cells (APCs) and myeloid-derived suppressor cells (MDSCs) play opposing roles to orchestrate innate and adaptive immune responses during physiological and pathological conditions. We investigated the role of DNA methylation in regulating the transcription of inhibitory/suppressive molecules in myeloid suppressive cells (identified as CD33+HLA-DR–) in comparison to APCs. We selected a number of immune checkpoints (ICs), IC ligands, and immunosuppressive molecules that have been implicated in MDSC function, including PD-L1, TIM-3, VISTA, galectin-9, TGF-β, ARG1 and MMP9. We examined their mRNA expression levels, and investigated whether DNA methylation regulates their transcription in sorted myeloid cell subpopulations. We found that mRNA levels of PD-L1, TIM-3, TGF-β, ARG1 and MMP9 in CD33+HLA-DR– cells were higher than APCs. However, VISTA and galectin-9 mRNA levels were relatively similar in both myeloid subpopulations. CpG islands in the promoter regions of TGF-β1, TIM-3 and ARG1 were highly unmethylated in CD33+HLA-DR–cells, compared with APCs, suggesting that DNA methylation is one of the key mechanisms, which regulate their expression. However, we did not find differences in the methylation status of PD-L1 and MMP9 between CD33+HLA-DR– and APCs, suggesting that their transcription could be regulated via other genetic and epigenetic mechanisms. The promoter methylation status of VISTA was relatively similar in both myeloid subpopulations. This study provides novel insights into the epigenetic mechanisms, which control the expression of inhibitory/suppressive molecules in circulating CD33+HLA-DR– cells in a steady-state condition, possibly to maintain immune tolerance and haemostasis.
- Subjects :
- DNA methylation
immunosuppression
B7 Antigens
epigenetics
Arginase
MDSC
Sialic Acid Binding Ig-like Lectin 3
Antigen-Presenting Cells
HLA-DR Antigens
B7-H1 Antigen
Epigenesis, Genetic
Matrix Metalloproteinase 9
Genetic Loci
Transforming Growth Factor beta
Humans
Myeloid Cells
Promoter Regions, Genetic
Hepatitis A Virus Cellular Receptor 2
Research Article
Research Paper
Subjects
Details
- Language :
- English
- ISSN :
- 15592308 and 15592294
- Volume :
- 15
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Epigenetics
- Accession number :
- edsair.pmid..........ecaa90835a01ec2c88ae09e7ffeec150