Han Sun Murray, Na Hye Young, Ham Onju, Choi Wanho, Sohn Moah, Ryu Seul Hye, In Hyunju, Hwang Ki-Chul, Park Chae Gyu
Laboratory 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.
Laboratory of Immunology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, Korea.
Immune Netw. 2016 Feb;16(1):61-74. doi: 10.4110/in.2016.16.1.61. Epub 2016 Feb 25.
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).
树突状细胞(DCs)是专业的抗原呈递细胞,它们摄取周围环境中的抗原,并将抗原呈递给未成熟的T淋巴细胞,以引发随后的抗原特异性免疫反应。DCs存在多种不同的亚群,包括浆细胞样DCs(pDCs)和经典DCs(cDCs),后者又由cDC1和cDC2谱系组成。尽管已经了解了DC特异性转录因子在不同DC亚群中的作用,但调节DC发育的转录后机制仍有待阐明。微小RNA(miRNAs)是众多生物过程中基因表达的关键转录后调节因子,但其对免疫系统的贡献才刚刚开始显现。在本研究中,我们筛选了内部探针集,通过靶向相关小鼠转录因子的转录本来鉴定可能参与DC发育和功能的miRNAs。用Flt3配体培养小鼠骨髓来源的DC亚群,发现miR-124高表达,它能够靶向TCF4的转录本,TCF4是一种对pDCs的发育和稳态至关重要的转录因子。对从小鼠体外培养物中分离以及通过体外纯化得到的DC亚群进行进一步的表达谱分析,结果表明,与pDCs和CD172α(+) cDC2细胞相比,miR-124在CD24(+) cDC1细胞中显著高表达。这些结果表明,miR-124可能通过对转录因子的转录后调控参与DC亚群的发育过程。