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TCF4-Targeting miR-124 is Differentially Expressed amongst Dendritic Cell Subsets
Sun Murray Han1, Hye Young Na2, Onju Ham3
1Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, Korea.; Brain Korea 21 PLUS Project for Medical Science, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, Korea.
MicroRNAs regulate dendritic cell (DC) development. miR-124 targets TCF4, impacting pDC homeostasis, and is highly expressed in cDC1 cells, suggesting a role in DC subset development.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Dendritic cells (DCs) are crucial antigen-presenting cells with distinct subpopulations like pDCs, cDC1, and cDC2.
- While transcription factors regulating DC subsets are known, posttranscriptional regulation, including microRNAs (miRNAs), remains underexplored.
- miRNAs are key posttranscriptional regulators with emerging roles in immune system development and function.
Purpose of the Study:
- To identify miRNAs involved in dendritic cell development and function.
- To investigate the role of specific miRNAs in regulating transcription factors critical for DC subset homeostasis.
- To elucidate the posttranscriptional mechanisms governing dendritic cell subset development.
Main Methods:
- Screening of an in-house probe collection to identify potential miRNA targets.
- Culture of mouse bone marrow with Flt3 ligand to examine DC subsets.
- Expression profiling of mouse DC subsets (in vitro and ex vivo) using techniques like flow cytometry.
Main Results:
- High expression of miR-124 was identified in dendritic cell subsets cultured with Flt3 ligand.
- miR-124 was found to directly target the transcript of TCF4, a transcription factor essential for plasmacytoid DC (pDC) development and homeostasis.
- miR-124 demonstrated significantly higher expression in CD24(+) classical DC1 (cDC1) cells compared to pDCs and CD172α(+) classical DC2 (cDC2) cells.
Conclusions:
- miR-124 plays a significant role in regulating dendritic cell subset development.
- The posttranscriptional targeting of TCF4 by miR-124 influences pDC homeostasis.
- Differential expression of miR-124 across DC subsets suggests its involvement in specifying cDC1 lineage identity.
