TCF4-Targeting miR-124 is Differentially Expressed amongst Dendritic Cell Subsets

Abstract

Dendritic cells (DCs) are professional antigen-presenting cells that sample their environment and present antigens to naïve T lymphocytes for the subsequent antigen-specific immune responses. DCs exist in a range of distinct subpopulations including plasmacytoid DCs (pDCs) and classical DCs (cDCs), with the latter consisting of the cDC1 and cDC2 lineages. Although the roles of DC-specific transcription factors across the DC subsets have become understood, the posttranscriptional mechanisms that regulate DC development are yet to be elucidated. MicroRNAs (miRNAs) are pivotal posttranscriptional regulators of gene expression in a myriad of biological processes, but their contribution to the immune system is just beginning to surface. In this study, our in-house probe collection was screened to identify miRNAs possibly involved in DC development and function by targeting the transcripts of relevant mouse transcription factors. Examination of DC subsets from the culture of mouse bone marrow with Flt3 ligand identified high expression of miR-124 which was able to target the transcript of TCF4, a transcription factor critical for the development and homeostasis of pDCs. Further expression profiling of mouse DC subsets isolated from in vitro culture as well as via ex vivo purification demonstrated that miR-124 was outstandingly expressed in CD24+ cDC1 cells compared to in pDCs and CD172α+ cDC2 cells. These results imply that miR-124 is likely involved in the processes of DC subset development by posttranscriptional regulation of a transcription factor(s).

Identifying Cattle Breed-Specific Partner Choice of Transcription Factors during the African Trypanosomiasis Disease Progression Using Bioinformatics Analysis

“…The factor TCF4 present in the network of N'Dama, belongs to a basic helix-loop-helix family which plays an integral role in Wnt signalling and neuronal differentiation especially in the brain development [146][147][148][149][150]. Furthermore, TCF4 is also involved in the immune responses through the production of plasmacytoid Dendritic Cells (pDCs), which respond to viral nucleic acids and autoimmune diseases, by the secretion of cytokines such as type I interferons [151][152][153][154]. Genetic alterations in TCF4 are easy targets and therefore mutations in TCF4 have been reported in the most common form of lymphoma which is the diffuse large B-cell lymphoma and Angelman syndrome [155,156].…”

Skin-Specific CD301b+ Dermal Dendritic Cells Drive IL-17−Mediated Psoriasis-Like Immune Response in Mice

“…Mice were subcutaneously injected with either daily 10 mg mouse FLT3L or phosphate buffered saline nine times and tissues were analyzed 24 hours after the last injection, as described in our previous studies (Darrasse-Jeze et al, 2009;Han et al, 2016). B16 mouse melanoma cells and B16-GM-CSF cells (kindly provided by Sang Jun Ha at Yonsei University) were cultured in complete DMEM containing 10% fetal bovine serum (Gibco, Carlsbad, CA) (Dranoff et al, 1993).…”

miRNA-124 in Immune System and Immune Disorders

“…DC subsets from the culture of mouse bone marrow showed high expression of miR-124, which is dominantly expressed in CD24(+) cDC1 cells compared with pDCs and CD172α + cDC2 cells. miR-124 is supposed to be involved in the processes of DC subset development by targeting the transcript of TCF4, a critical transcription factor in the development and homeostasis of pDCs ( 17 ).…”