AI Article Synopsis
- Monocytes are vital for the immune system, and this study investigates how chromatin remodeling affects their differentiation into various effector cell types, particularly dendritic cells.
- The research identifies that the lysine methyltransferase KMT1c is notably upregulated during the differentiation of monocytes into immature dendritic cells (iDCs), and inhibiting KMT1c alters transcription of the DC marker DC-SIGN.
- The findings suggest that KMTs play a crucial role in monocyte-derived dendritic cell differentiation, highlighting the potential of KMT inhibitors in epigenetic immune therapies, which traditionally focus on HDAC inhibitors.
Article Abstract
Monocytes play a key role in immune system function. Chromatin remodeling is crucial for various differentiation and gene regulation processes and is rather well studied in T cells. However, for monocytes not much is known regarding how the epigenetic machinery influences the differentiation into various effector cell types. In the work presented here, we explore the epigenetic underpinnings of monocyte differentiation. By transcriptional profiling we show that transcription of lysine methyltransferases (KMTs) and in particular KMT1c is markedly up regulated after differentiation of monocytes into immature dendritic cells (iDCs). Specifically inhibiting KMT1c function, using the small-molecule inhibitor BIX-01294, changes the transcription levels of the DC marker DC-SIGN, but does not affect surface protein expression. Blocking global KMT activity, using DZNep, does influence monocyte differentiation into iDCs, indicated by a loss of DC-SIGN surface expression. When BIX-01294 and DZNep treatment was combined DC-SIGN expression was almost lost completely. This work shows that the activities of KMTs are required for successful differentiation of monocyte-derived dendritic cells. Furthermore it shows the importance of KMT inhibitors in the field of epigenetic immune therapy, which is still much focused around HDAC inhibitors.
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| http://dx.doi.org/10.1016/j.humimm.2015.03.017 | DOI Listing |
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